This study is designed to evaluate safety and antitumor activity of U3-1402 in two parts: Dose Escalation and Dose Expansion. In Dose Escalation, U3-1402 will be evaluated in participants with metastatic or unresectable NSCLC with epidermal growth factor receptor (EGFR) activating mutation after disease progression during/after EGFR tyrosine kinase inhibitor (TKI) therapy. In Dose Expansion, U3-1402 will be evaluated in participants with metastatic or unresectable NSCLC with EGFR activating mutation or squamous or non-squamous NSCLC (ie, without EGFR-activating mutations) with disease progression during/after systemic treatment for locally advanced or metastatic disease.

NCT03260491

Conditions

1. Non-Small Cell Lung Cancer (NSCLC)

Interventions

1. Drug: U3-1402

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R --- --- L861Q ---

3. Has documentation of EGFR-activating mutation(s) detected from tumor tissue: G719X, exon deletion 19, L858R, or L861Q. --- L858R --- --- L861Q ---

Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R --- --- L861Q ---

Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Inclusion Criteria for both Dose Escalation and Dose Expansion: 1. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 2. Has at least one measurable lesion per RECIST version 1.1 3. Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening Inclusion Criteria for Dose Escalation only: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011) 1. Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1] or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 3. Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib 4. Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening 5. Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib 6. --- L858R --- --- L861Q --- --- L858R --- --- L861Q ---

Has clinically significant corneal disease Additional Exclusion Criteria for Dose Expansion Cohort 2: 1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon 19 deletion, L858R, or L861Q Non-Small Cell Lung Cancer (NSCLC) Lung Neoplasms Carcinoma, Non-Small-Cell Lung The primary objectives are: - For Dose Escalation, to assess the safety and tolerability of U3-1402 in the study population and to determine the recommended dose for expansion (RDE) of U3-1402 in the study population - For Dose Expansion, to investigate the antitumor activity of U3-1402 The number of treatment cycles is not fixed in this study. --- L858R --- --- L861Q ---

A phase II, open-label, multicenter, single-arm, prospective clinical study to investigate the efficacy and safety of tislelizumab (anti-pd1 antibody) combined with chemotherapy in non-squamous non-small cell lung cancer patients with EGFR sensitizing mutation who failed EGFR TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) therapy.

NCT04405674

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: Tislelizumab
2. Drug: Carboplatin and Nab-paclitaxel
3. Drug: Pemetrexed

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

2. Documentation of tumor EGFR sensitizing mutation before EGFR TKI treatment, including 19del, L858R, G719X, S786I and L861Q. --- L858R --- --- S786I --- --- L861Q ---

This is a Phase 2, open-label study to evaluate PD-1 inhibitor JTX-4014 alone and in combination with vopratelimab, an ICOS agonist, in biomarker-selected adult subjects with metastatic NSCLC who are PD-1/PD-L1 inhibitor naïve and have progressed on a platinum based chemotherapy regimen.

NCT04549025

Conditions

1. NSCLC

Interventions

1. Drug: JTX-4014
2. Drug: Vopratelimab

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- Current or past participation in a study of an investigational agent or using an investigational device in the metastatic setting - Chemotherapy < 28 days prior to planned C1D1 - Prior immunotherapy including, but not limited to PD-1 or PD-L1 inhibitor mAb at any time, including JTX-4014; therapy with any mAb that specifically binds to ICOS, including vopratelimab; or chimeric antigen receptor T cell therapy - Use of anticancer therapies listed below in the metastatic setting (allowed as prior treatment for localized disease): 1. Biologic therapy 2. Targeted small molecule therapy 3. Organ transplantation, including allogeneic or autologous stem cell transplantation - Positive test for any of the following epidermal growth factor receptor gene mutations in blood or tumor: Exon 18 G719A; Exon 18 G719C; Exon 18 G719S; Exon 19 Del; Exon 20 S768I; Exon 20 T790M; Exon 20 Ins; Exon 21 L858R; Exon 21 L861Q - Prior whole brain radiation Inclusion Criteria: - Able and willing to participate and comply with all study requirements - Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) with evaluable or measurable disease according to RECIST v1.1 with at least 1 measurable lesion - Confirmed tumor RNA signature score - Experienced progression of locally advanced or metastatic NSCLC after 1 prior systemic antineoplastic platinum-containing regimen (adjuvant therapy will count as a regimen if administered within 1 year before the relapse) - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Predicted life expectancy of ≥ 3 months - Adequate organ function - WOCBP must agree to use highly effective birth control Exclusion Criteria: - Concurrent anticancer treatment or subject is expected to require any other form of antineoplastic therapy while on study, either approved or investigational. --- G719A --- --- G719C --- --- G719S --- --- S768I --- --- T790M --- --- L858R --- --- L861Q ---

- Current or past participation in a study of an investigational agent or using an investigational device in the metastatic setting - Chemotherapy < 28 days prior to planned C1D1 - Prior immunotherapy including, but not limited to PD-1 or PD-L1 inhibitor mAb at any time, including JTX-4014; therapy with any mAb that specifically binds to ICOS, including vopratelimab; or chimeric antigen receptor T cell therapy - Use of anticancer therapies listed below in the metastatic setting (allowed as prior treatment for localized disease): 1. Biologic therapy 2. Targeted small molecule therapy 3. Organ transplantation, including allogeneic or autologous stem cell transplantation - Positive test for any of the following epidermal growth factor receptor gene mutations in blood or tumor: Exon 18 G719A; Exon 18 G719C; Exon 18 G719S; Exon 19 Del; Exon 20 S768I; Exon 20 T790M; Exon 20 Ins; Exon 21 L858R; Exon 21 L861Q - Prior whole brain radiation NSCLC Carcinoma, Non-Small-Cell Lung JTX-4014 is a fully human IgG4 monoclonal antibody designed to specifically bind to PD-1 and block its interaction with its ligands, PD-L1 and PD-L2, to augment anti-tumor T cell activity. --- G719A --- --- G719C --- --- G719S --- --- S768I --- --- T790M --- --- L858R --- --- L861Q ---

Lung cancer is the leading cause of cancer deaths. Advances in the systemic treatment of non-small cell lung cancer (NSCLC) have increased survival in metastatic EGFR-mutated NSCLC. However resistance to therapy can develop. NSCLC tumors with EGFR-activating mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors with overall response rates approximating 80%. The third generation EGFR compound osimertinib is a standard first line option. Resistance to the third generation EGFR-TKI osimertinib can develop with a median PFS of 18.9 months. Current research examining acquired resistance to EGFR-TKIs has focused on overcoming these main mechanisms of EGFR-TKI resistance and understanding the impact of co-occurring alterations. Frequently altered pathways concomitantly affected with EGFR in lung cancer are cell cycle genes. This study will explore a strategy to inhibit EGFR and CD4/6 in resistant EGFR mutated lung cancer patients post progression on osimertinib.

NCT04545710

Conditions

1. Lung Cancer

Interventions

1. Drug: Abemaciclib
2. Drug: Osimertinib

MeSH:Lung Neoplasms

HPO:Neoplasm of the lung

- Tumor must harbor an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion, Exon 18 G719X, Exon 21 L861Q). --- L858R --- --- L861Q ---

The purpose of this study is to evaluate the safety and tolerability of itacitinib in combination with osimertinib in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC).

NCT02917993

Conditions

1. Lung Cancer

Interventions

1. Drug: Itacitinib
2. Drug: Osimertinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Documented evidence of somatic activating mutation in EGFR (eg, G719X, exon 19 deletion, L858R, L861Q) in a tumor tissue sample. --- L858R --- --- L861Q ---

This phase Ib trial studies the side effects and best dose of osimertinib and navitoclax when given together and to see how well they work in treating patients with previously treated epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer that has spread to other places in the body (metastatic) or has not responded to previous treatment with initial EGFR kinase inhibitor. Osimertinib and navitoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT02520778

Conditions

1. Advanced Lung Non-Squamous Non-Small Cell Carcinoma
2. Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
3. Stage III Lung Non-Small Cell Cancer AJCC v7
4. Stage IIIA Lung Non-Small Cell Cancer AJCC v7
5. Stage IIIB Lung Non-Small Cell Cancer AJCC v7
6. Stage IV Lung Non-Small Cell Cancer AJCC v7

Interventions

1. Drug: Navitoclax
2. Drug: Osimertinib

MeSH:Carcinoma Carcinoma, Non-Small-Cell Lung

HPO:Carcinoma Non-small cell lung carcinoma

Biomarkers of apoptosis such as BCL-XL and BIM levels will be measured in tumor tissue and correlated with response in an exploratory fashion, under the hypothesis that navitoclax will have greater activity in cancers with high BCL-XL levels and inadequate apoptotic response.. Inclusion Criteria: - Histologically confirmed non-squamous NSCLC, with incurable advanced or metastatic disease - Prior genotyping positive for an EGFR activating mutation (L858R, exon 19 deletion, G719X, L861Q) - Progression after prior treatment with an EGFR TKI; in addition to this one prior line of therapy, any additional prior lines of therapy are permitted; prior treatment with a third-generation EGFR TKI is allowed for the dose escalation phase, but is not permitted for the expansion cohort - Adequate archival tissue from a biopsy performed after progression of disease on previous EGFR TKI; or willing to undergo a new tumor biopsy prior to registration (for the dose escalation portion only this requirement can be waived if T790M status has already been determined using a local assay) - For the dose expansion portion only, patient must: 1) have a tumor which is EGFR-T790M positive and 2) be treatment naive to T790M-directed EGFR TKI (e.g. --- L858R --- --- L861Q ---

AZD9291, rociletinib, etc); T790M testing may be done locally or centrally on study, but if done locally, tissue must be available for central confirmation - Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - Any number of prior therapies are allowed - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) - Patients must have the ability to swallow oral dosage forms - Life expectancy of greater than 3 months - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Hemoglobin >= 8.0 g/dL - Platelets >= 100,000/mcL - Activated partial thromboplastin time (aPTT), prothrombin time (PT) =< 1.2 x upper limit of normal (ULN) - Total bilirubin =< 1.5 x ULN (patients with Gilbert's syndrome may have serum bilirubin > 1.5 x ULN) - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN - Creatinine =< 2.0 mg/dL OR - Creatinine clearance >= 50 mL/min - The effects of AZD9291 and navitoclax on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception using one of the methods listed below prior to study entry, for the duration of study participation, and for 3 months for women and 6 months for men following the date of the last dose of AZD9291 and/or navitoclax: - Total abstinence from sexual intercourse (minimum one complete menstrual cycle prior to study drug administration) - Vasectomized male subject or vasectomized partner of female subjects - Hormonal contraceptives (oral, parenteral, transdermal or vaginal ring) for at least 3 months prior to study drug administration; if the subject is currently using a hormonal contraceptive, she should also use a barrier method during this study and for 3 months after study completion - Intrauterine device (IUD) - Double-barrier method: male condom plus diaphragm or vaginal cap with spermicide (contraceptive sponge, jellies or creams) - Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and 6 months following completion of therapy - Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to initiation of treatment; women will be considered not of childbearing potential if they are surgically sterile (bilateral oophorectomy or hysterectomy) and/or post-menopausal (amenorrheic for at least 12 months) - Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately - Patients with a prior history of brain metastases are eligible provided: - The brain metastases have been treated - The patient is asymptomatic from the brain metastases - Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration - The brain metastases are stable on pre-registration imaging - Patients must have completed last chemotherapy >= 3 weeks or radiotherapy >= 2 weeks prior to receiving study drugs - Patients must have recovered from adverse events attributable to previous treatment to =< grade 1, except for alopecia and sensory neuropathy =< grade 2 - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Major surgery within 21 days of starting protocol treatment - Patients must discontinue previous EGFR-TKI at least 7 days prior to study enrollment - Patients who are receiving any other investigational agents - Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease - Patients currently receiving (or unable to stop use at least 1 week prior to receiving the 1st dose of AZD9291) medications or herbal supplements known to be potent inhibitors of cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; patients are eligible if they stop use of these compounds at least 1 week prior to receiving any treatment on this protocol - Patients receiving anticoagulation or anti-platelet therapy are excluded due to the risk of thrombocytopenia with navitoclax; excluded agents include heparin or low molecular weight heparin, warfarin, clopidogrel, ibuprofen and other nonsteroidal anti-inflammatory drug (NSAIDS), tirofiban, and other anticoagulants, drugs, or herbal supplements that affect platelet function; administration of heparin to keep subject's infusion lines patent is allowed; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are allowed; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention, may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor - Patients with an underlying condition predisposing them to bleeding or currently exhibiting signs of clinically significant bleeding - Patients with a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drug - Patients with a significant history of cardiovascular disease (e.g., myocardial infarction [MI], thrombotic or thromboembolic event in the last 6 months) - Any of the following cardiac criteria: - Mean resting corrected QT interval (QTc using Frederica's formula [QTcF]) > 470 msec - Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block) - Congenital long QT syndrome or family history of long QT syndrome - Patients with active malignancies other than NSCLC or patients with prior curatively treated malignancy at high risk of relapse during the study period with the exception of localized squamous or basal cell skin cancers - Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, gastrointestinal disease limiting absorption of AZD9291 such as a malabsorption syndrome or inflammatory bowel disease or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study because AZD9291 and navitoclax have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD9291 and navitoclax, breastfeeding should be discontinued if the mother is treated with AZD9291 and navitoclax - History of hypersensitivity to AZD9291 (or drugs with a similar chemical structure or class to AZD9291) or any excipients of these agents - Patients with human immunodeficiency virus (HIV) on antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD9291 Inclusion Criteria: - Histologically confirmed non-squamous NSCLC, with incurable advanced or metastatic disease - Prior genotyping positive for an EGFR activating mutation (L858R, exon 19 deletion, G719X, L861Q) - Progression after prior treatment with an EGFR TKI; in addition to this one prior line of therapy, any additional prior lines of therapy are permitted; prior treatment with a third-generation EGFR TKI is allowed for the dose escalation phase, but is not permitted for the expansion cohort - Adequate archival tissue from a biopsy performed after progression of disease on previous EGFR TKI; or willing to undergo a new tumor biopsy prior to registration (for the dose escalation portion only this requirement can be waived if T790M status has already been determined using a local assay) - For the dose expansion portion only, patient must: 1) have a tumor which is EGFR-T790M positive and 2) be treatment naive to T790M-directed EGFR TKI (e.g. --- T790M --- --- L858R --- --- L861Q ---

A Phase I, Open-Label, Two Parts Study to Assess the Safety, Tolerability,Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Chinese Patients with Advanced Non-Small Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent Study Objective: 1, Primary Objective To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550) after single then multiple doses of AZD9291 administered orally once daily in Chinese patients with locally advanced or metastatic non small cell lung Cancer (NSCLC) who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) agent. 2, Secondary objective(s) To investigate the safety and tolerability of AZD9291 when given orally to Chinese patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an approved EGFR TKI agent. To obtain a preliminary assessment of the anti-tumour activity of AZD9291 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.

NCT02529995

Conditions

1. Carcinoma, Non-Small-Cell Lung With EGFR Mutation Positive

Interventions

1. Drug: AZD9291 40 mg
2. Drug: AZD9291 80 mg

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

In addition other lines of therapy may have been given - Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 6. World Health Organisation (WHO) performance status 0-1 7. --- L858R --- --- L861Q ---

This phase I/II trial studies the side effects and best dose of onalespib lactate when given together with erlotinib hydrochloride and to see how well they work in treating patients with EGFR-mutant non-small cell lung cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Erlotinib hydrochloride and onalespib lactate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT02535338

Conditions

1. Recurrent Lung Non-Small Cell Carcinoma
2. Stage IV Lung Non-Small Cell Cancer AJCC v7

Interventions

1. Drug: Erlotinib Hydrochloride
2. Other: Laboratory Biomarker Analysis
3. Drug: Onalespib Lactate
4. Other: Pharmacological Study

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Progression-free survival will be summarized for both cohorts as time from first protocol treatment, using the product-limit, Kaplan-Meier, estimator.. Inclusion Criteria: - PHASE I: Patients must have metastatic/recurrent, histologically confirmed NSCLC that harbors an EGFR activating mutation (exon 21 L858R, exon 19 deletion, exon 18 G719X, exon 21 L861Q) with progressive disease by RECIST 1.1 on a previous EGFR-tyrosine kinase inhibitor (TKI); OR patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR exon 20 insertion with progressive disease on platinum containing chemotherapy - PHASE II COHORT A: Patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR activating mutation (exon 21 L858R, exon 19 deletion, exon 18 G719X, exon 21 L861Q) with stable disease by RECIST 1.1 as best response on erlotinib compared to pre-treatment erlotinib imaging by RECIST 1.1 or progressive disease compared to pre-treatment imaging by RECIST 1.1 after a minimum duration of treatment on erlotinib of 12-weeks; patients must be enrolled within 6 months of initiation of erlotinib - PHASE II COHORT B: Patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR exon 20 insertion with progressive disease on or after platinum doublet chemotherapy - FOR PHASE I: If patient is on erlotinib at the time of signed consent, the patient does NOT need to be discontinued prior to initiation of erlotinib and onalespib; other EGFR-TKIs must be discontinued at least 7 days prior to initiation of erlotinib and onalespib - FOR PHASE II COHORT A: If patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to receiving treatment erlotinib and onalespib; last dose of erlotinib must be less than 28 days from when patient signs consent - FOR PHASE II COHORT B: (EGFR exon 20 insertions): Prior EGFR-TKIs including erlotinib is allowed; if patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to initiation of erlotinib and onalespib - Local testing for EGFR-mutations for this study is acceptable provided it was performed in a Clinical Laboratory Improvement Act (CLIA) certified lab - Patients with a prior history of brain metastases are eligible provided: - The brain metastases have been treated - The patient is asymptomatic from the brain metastases - Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration - Patients must have completed last chemotherapy >= 3 weeks or radiotherapy >= 2 weeks prior to receiving study drugs - Patients must have recovered from adverse events attributable to previous treatment to =< grade 1, except for alopecia and sensory neuropathy =< grade 2 - Measurable disease by RECIST 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >= 100,000/mcL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal - Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 --- L858R --- --- L861Q ---

Progression-free survival will be summarized for both cohorts as time from first protocol treatment, using the product-limit, Kaplan-Meier, estimator.. Inclusion Criteria: - PHASE I: Patients must have metastatic/recurrent, histologically confirmed NSCLC that harbors an EGFR activating mutation (exon 21 L858R, exon 19 deletion, exon 18 G719X, exon 21 L861Q) with progressive disease by RECIST 1.1 on a previous EGFR-tyrosine kinase inhibitor (TKI); OR patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR exon 20 insertion with progressive disease on platinum containing chemotherapy - PHASE II COHORT A: Patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR activating mutation (exon 21 L858R, exon 19 deletion, exon 18 G719X, exon 21 L861Q) with stable disease by RECIST 1.1 as best response on erlotinib compared to pre-treatment erlotinib imaging by RECIST 1.1 or progressive disease compared to pre-treatment imaging by RECIST 1.1 after a minimum duration of treatment on erlotinib of 12-weeks; patients must be enrolled within 6 months of initiation of erlotinib - PHASE II COHORT B: Patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR exon 20 insertion with progressive disease on or after platinum doublet chemotherapy - FOR PHASE I: If patient is on erlotinib at the time of signed consent, the patient does NOT need to be discontinued prior to initiation of erlotinib and onalespib; other EGFR-TKIs must be discontinued at least 7 days prior to initiation of erlotinib and onalespib - FOR PHASE II COHORT A: If patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to receiving treatment erlotinib and onalespib; last dose of erlotinib must be less than 28 days from when patient signs consent - FOR PHASE II COHORT B: (EGFR exon 20 insertions): Prior EGFR-TKIs including erlotinib is allowed; if patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to initiation of erlotinib and onalespib - Local testing for EGFR-mutations for this study is acceptable provided it was performed in a Clinical Laboratory Improvement Act (CLIA) certified lab - Patients with a prior history of brain metastases are eligible provided: - The brain metastases have been treated - The patient is asymptomatic from the brain metastases - Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration - Patients must have completed last chemotherapy >= 3 weeks or radiotherapy >= 2 weeks prior to receiving study drugs - Patients must have recovered from adverse events attributable to previous treatment to =< grade 1, except for alopecia and sensory neuropathy =< grade 2 - Measurable disease by RECIST 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >= 100,000/mcL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal - Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 --- L858R --- --- L861Q --- --- L858R --- --- L861Q ---

m^2 for patients with creatinine levels above institutional normal - Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.3 upper limit of normal (ULN) - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of erlotinib and/or onalespib administration - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Patients who are receiving any other investigational agents - History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib and/or onalespib - History of pneumonitis attributed to an EGFR inhibitor; history of radiation pneumonitis is allowed provided steroid administration for pneumonitis was not required - Mean resting corrected QT interval (QTc using Fridericia's formula [QTcF]) > 470 msec - Left ventricular ejection fraction =< 50% as demonstrated by echocardiogram or multigated acquisition scan (MUGA) - Drugs that are known to increase torsades de pointes should be avoided; patients must discontinue these medications prior to enrollment on study; selection of alternate concomitant medications with no or minimal torsades de pointes potential is recommended - Strong CYP3A4 inducers and inhibitors should be avoided; selection of alternate concomitant medications with no or minimal CYP3A4 enzyme inhibition potential is recommended; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with erlotinib and onalespib - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible - Prior treatment with a Hsp90 inhibitor - Treatment with proton pump inhibitors within 3 days prior to study entry; if treatment with an histamine (H2)-receptor antagonist such as ranitidine is required, erlotinib must be taken 10 hours after the H2-receptor antagonist dosing and at least 2 hours before the next dose of the H2-receptor antagonist; although the effect of antacids on erlotinib pharmacokinetics has not been evaluated, the antacid dose and the erlotinib dose should be separated by several hours, if an antacid is necessary - Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test) Inclusion Criteria: - PHASE I: Patients must have metastatic/recurrent, histologically confirmed NSCLC that harbors an EGFR activating mutation (exon 21 L858R, exon 19 deletion, exon 18 G719X, exon 21 L861Q) with progressive disease by RECIST 1.1 on a previous EGFR-tyrosine kinase inhibitor (TKI); OR patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR exon 20 insertion with progressive disease on platinum containing chemotherapy - PHASE II COHORT A: Patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR activating mutation (exon 21 L858R, exon 19 deletion, exon 18 G719X, exon 21 L861Q) with stable disease by RECIST 1.1 as best response on erlotinib compared to pre-treatment erlotinib imaging by RECIST 1.1 or progressive disease compared to pre-treatment imaging by RECIST 1.1 after a minimum duration of treatment on erlotinib of 12-weeks; patients must be enrolled within 6 months of initiation of erlotinib - PHASE II COHORT B: Patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR exon 20 insertion with progressive disease on or after platinum doublet chemotherapy - FOR PHASE I: If patient is on erlotinib at the time of signed consent, the patient does NOT need to be discontinued prior to initiation of erlotinib and onalespib; other EGFR-TKIs must be discontinued at least 7 days prior to initiation of erlotinib and onalespib - FOR PHASE II COHORT A: If patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to receiving treatment erlotinib and onalespib; last dose of erlotinib must be less than 28 days from when patient signs consent - FOR PHASE II COHORT B: (EGFR exon 20 insertions): Prior EGFR-TKIs including erlotinib is allowed; if patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to initiation of erlotinib and onalespib - Local testing for EGFR-mutations for this study is acceptable provided it was performed in a Clinical Laboratory Improvement Act (CLIA) certified lab - Patients with a prior history of brain metastases are eligible provided: - The brain metastases have been treated - The patient is asymptomatic from the brain metastases - Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration - Patients must have completed last chemotherapy >= 3 weeks or radiotherapy >= 2 weeks prior to receiving study drugs - Patients must have recovered from adverse events attributable to previous treatment to =< grade 1, except for alopecia and sensory neuropathy =< grade 2 - Measurable disease by RECIST 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >= 100,000/mcL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal - Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 --- L858R --- --- L861Q ---

m^2 for patients with creatinine levels above institutional normal - Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.3 upper limit of normal (ULN) - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of erlotinib and/or onalespib administration - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Patients who are receiving any other investigational agents - History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib and/or onalespib - History of pneumonitis attributed to an EGFR inhibitor; history of radiation pneumonitis is allowed provided steroid administration for pneumonitis was not required - Mean resting corrected QT interval (QTc using Fridericia's formula [QTcF]) > 470 msec - Left ventricular ejection fraction =< 50% as demonstrated by echocardiogram or multigated acquisition scan (MUGA) - Drugs that are known to increase torsades de pointes should be avoided; patients must discontinue these medications prior to enrollment on study; selection of alternate concomitant medications with no or minimal torsades de pointes potential is recommended - Strong CYP3A4 inducers and inhibitors should be avoided; selection of alternate concomitant medications with no or minimal CYP3A4 enzyme inhibition potential is recommended; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with erlotinib and onalespib - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible - Prior treatment with a Hsp90 inhibitor - Treatment with proton pump inhibitors within 3 days prior to study entry; if treatment with an histamine (H2)-receptor antagonist such as ranitidine is required, erlotinib must be taken 10 hours after the H2-receptor antagonist dosing and at least 2 hours before the next dose of the H2-receptor antagonist; although the effect of antacids on erlotinib pharmacokinetics has not been evaluated, the antacid dose and the erlotinib dose should be separated by several hours, if an antacid is necessary - Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test) Inclusion Criteria: - PHASE I: Patients must have metastatic/recurrent, histologically confirmed NSCLC that harbors an EGFR activating mutation (exon 21 L858R, exon 19 deletion, exon 18 G719X, exon 21 L861Q) with progressive disease by RECIST 1.1 on a previous EGFR-tyrosine kinase inhibitor (TKI); OR patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR exon 20 insertion with progressive disease on platinum containing chemotherapy - PHASE II COHORT A: Patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR activating mutation (exon 21 L858R, exon 19 deletion, exon 18 G719X, exon 21 L861Q) with stable disease by RECIST 1.1 as best response on erlotinib compared to pre-treatment erlotinib imaging by RECIST 1.1 or progressive disease compared to pre-treatment imaging by RECIST 1.1 after a minimum duration of treatment on erlotinib of 12-weeks; patients must be enrolled within 6 months of initiation of erlotinib - PHASE II COHORT B: Patients must have metastatic/recurrent histologically confirmed NSCLC that harbors an EGFR exon 20 insertion with progressive disease on or after platinum doublet chemotherapy - FOR PHASE I: If patient is on erlotinib at the time of signed consent, the patient does NOT need to be discontinued prior to initiation of erlotinib and onalespib; other EGFR-TKIs must be discontinued at least 7 days prior to initiation of erlotinib and onalespib - FOR PHASE II COHORT A: If patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to receiving treatment erlotinib and onalespib; last dose of erlotinib must be less than 28 days from when patient signs consent - FOR PHASE II COHORT B: (EGFR exon 20 insertions): Prior EGFR-TKIs including erlotinib is allowed; if patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to initiation of erlotinib and onalespib - Local testing for EGFR-mutations for this study is acceptable provided it was performed in a Clinical Laboratory Improvement Act (CLIA) certified lab - Patients with a prior history of brain metastases are eligible provided: - The brain metastases have been treated - The patient is asymptomatic from the brain metastases - Corticosteroids prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration - Patients must have completed last chemotherapy >= 3 weeks or radiotherapy >= 2 weeks prior to receiving study drugs - Patients must have recovered from adverse events attributable to previous treatment to =< grade 1, except for alopecia and sensory neuropathy =< grade 2 - Measurable disease by RECIST 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Life expectancy of greater than 3 months - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >= 100,000/mcL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal - Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 --- L858R --- --- L861Q --- --- L858R --- --- L861Q ---

The primary goal is to evaluate the efficacy of osimertinib (AZD9291), in terms of the objective response rate in patients with advanced non-squamous NSCLC with EGFR mutations and the EGFR T790M mutation at diagnosis as defined by RECIST 1.1 criteria. Safety and efficacy will also be measured.

NCT02841579

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: Osimertinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally. --- L858R --- --- L861Q ---

- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment that have not been confirmed centrally. --- L858R --- --- L861Q ---

Hsp90 inhibitor AUY922 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase I/II trial is studying the side effects and best dose of Hsp90 inhibitor AUY922 when given together with erlotinib hydrochloride and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer.

NCT01259089

Conditions

1. Adenocarcinoma of the Lung
2. Non-small Cell Lung Cancer

Interventions

1. Drug: erlotinib hydrochloride
2. Drug: Hsp90 inhibitor AUY922
3. Other: laboratory biomarker analysis
4. Procedure: needle biopsy
5. Genetic: mutation analysis
6. Other: pharmacological study

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung Adenocarcinoma Adenocarcinoma of Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Overall Survival (OS) will be measured from treatment initiation until death due to any cause for patients with acquired resistance with T790M mutations in the phase II portion of the study.. Inclusion Criteria: - All patients must have pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically at NU, MSKCC, or DFCI and EITHER previous RECIST-defined response (CR or PR) to an EGFR-TKI (erlotinib or gefitinib) or an investigational EGFR TK inhibitor OR a documented mutation in the EGFR gene (G719X, exon 19 deletion, L858R, L861Q) - Radiographic progression by RECIST during treatment with erlotinib/gefitinib - Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time - Measurable (RECIST) indicator lesion not previously irradiated - Must have undergone a biopsy after the development of acquired resistance - Karnofsky Performance Status >= 70% OR ECOG/WHO Performance Status 0-1 - Signed informed consent - Effective contraception and negative serum pregnancy test obtained within two weeks prior to the first administration of AUY922 in all pre-menopausal women (ie., last menstrual period =< 24 months ago) and women < 2 years after onset of menopause; menopause is defined as the time at which fertility ceases, where a woman has had no menstruation for > 24 months - Total bilirubin =< 1.5 x Upper Limit of Normal (ULN) - AST/SGOT and ALT/SGPT =< 3.0 x ULN, or =< 5.0 x ULN if liver metastasis present - Absolute neutrophil count (ANC) >= 1.5 x10^9/L - Hemoglobin (Hgb) >= 9g/dL - Platelets (plts) >= 100 x 10^9/L - Serum creatinine =< 1.5 x ULN or 24 hour clearance >= 50 mL/min Exclusion Criteria: - Symptomatic CNS metastases which are symptomatic and /or requiring escalating doses of steroids - Prior treatment with any HSP90 inhibitor compounds - Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed) - Palliative radiation within 2 weeks - Unresolved diarrhea >= CTCAE grade 2 - Pregnant or lactating women - Women of childbearing potential (WCBP) (i.e. --- T790M --- --- L858R --- --- L861Q ---

Gilbert's syndrome) Inclusion Criteria: - All patients must have pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically at NU, MSKCC, or DFCI and EITHER previous RECIST-defined response (CR or PR) to an EGFR-TKI (erlotinib or gefitinib) or an investigational EGFR TK inhibitor OR a documented mutation in the EGFR gene (G719X, exon 19 deletion, L858R, L861Q) - Radiographic progression by RECIST during treatment with erlotinib/gefitinib - Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time - Measurable (RECIST) indicator lesion not previously irradiated - Must have undergone a biopsy after the development of acquired resistance - Karnofsky Performance Status >= 70% OR ECOG/WHO Performance Status 0-1 - Signed informed consent - Effective contraception and negative serum pregnancy test obtained within two weeks prior to the first administration of AUY922 in all pre-menopausal women (ie., last menstrual period =< 24 months ago) and women < 2 years after onset of menopause; menopause is defined as the time at which fertility ceases, where a woman has had no menstruation for > 24 months - Total bilirubin =< 1.5 x Upper Limit of Normal (ULN) - AST/SGOT and ALT/SGPT =< 3.0 x ULN, or =< 5.0 x ULN if liver metastasis present - Absolute neutrophil count (ANC) >= 1.5 x10^9/L - Hemoglobin (Hgb) >= 9g/dL - Platelets (plts) >= 100 x 10^9/L - Serum creatinine =< 1.5 x ULN or 24 hour clearance >= 50 mL/min Exclusion Criteria: - Symptomatic CNS metastases which are symptomatic and /or requiring escalating doses of steroids - Prior treatment with any HSP90 inhibitor compounds - Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed) - Palliative radiation within 2 weeks - Unresolved diarrhea >= CTCAE grade 2 - Pregnant or lactating women - Women of childbearing potential (WCBP) (i.e. --- L858R --- --- L861Q ---

This study has two parts: dose escalation and dose expansion. The primary objectives are: - For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with osimertinib in the study population - For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles. The number of treatment cycles is not fixed in this study. Participants will continue study treatment until they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity).

NCT03255083

Conditions

1. Non-small Cell Lung Cancer (NSCLC)

Interventions

1. Drug: DS-1205c
2. Drug: Osimertinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

3. Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011): 1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression (Response Evaluation Criteria in Solid Tumors [RECIST version 1.1] or World Health Organization [WHO]) while on continuous treatment with an EGFR TKI. 4. Is currently receiving, and is able to discontinue erlotinib, gefinitib, or afatinib; or is currently receiving osimertinib at the prescribed 80 mg dose and is able to interrupt osimertinib. --- L858R --- --- L861Q ---

CK-101 is a novel, potent, small molecule tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral CK-101; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral CK-101; to assess the safety and efficacy of CK-101 in treatment-naive NSCLC patients known to have activating EGFR mutations and previously treated NSCLC patients known to have the T790M EGFR mutation.

NCT02926768

Conditions

1. Lung Neoplasms
2. Carcinoma, Non-Small-Cell Lung
3. Lung Diseases
4. Adenocarcinoma

Interventions

1. Drug: CK-101

MeSH:Carcinoma, Non-Small-Cell Lung Lung Neoplasms Lung Diseases

HPO:Abnormal lung morphology Neoplasm of the lung Non-small cell lung carcinoma

Inclusion Criteria: - Measureable disease according to RECIST Version 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Minimum age of 18 years - Adequate hematological, hepatic and renal function - Written consent on an Institutional Review Board-approved informed consent form prior to any study-specific evaluation - Histologically or cytologically confirmed diagnosis of one of the following: 1. Metastatic or unresectable locally advanced NSCLC with documented evidence that the tumor harbors one of the two common EGFR mutations known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (exon 19 deletion, L858R), either alone or in combination with other EGFR mutations, determined by PCR-based testing of the tumor tissue or plasma sample, and without prior exposure to an EGFR-TKI therapy; OR 2. Metastatic or unresectable locally advanced NSCLC: 1. with documented evidence that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q); and 2. with evidence of radiological disease progression while on a previous continuous treatment with a first-generation EGFR TKI. --- L858R --- --- L858R --- --- L861Q ---

- Refusal to use adequate contraception for fertile patients (females and males) - Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study - Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection Inclusion Criteria: - Measureable disease according to RECIST Version 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Minimum age of 18 years - Adequate hematological, hepatic and renal function - Written consent on an Institutional Review Board-approved informed consent form prior to any study-specific evaluation - Histologically or cytologically confirmed diagnosis of one of the following: 1. Metastatic or unresectable locally advanced NSCLC with documented evidence that the tumor harbors one of the two common EGFR mutations known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (exon 19 deletion, L858R), either alone or in combination with other EGFR mutations, determined by PCR-based testing of the tumor tissue or plasma sample, and without prior exposure to an EGFR-TKI therapy; OR 2. Metastatic or unresectable locally advanced NSCLC: 1. with documented evidence that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q); and 2. with evidence of radiological disease progression while on a previous continuous treatment with a first-generation EGFR TKI. --- L858R --- --- L858R --- --- L861Q ---

This study will test if local therapies in addition to erlotinib can improve responses and delay the time until new treatment is required. This study will also collect blood samples for research blood tests.

NCT02450591

Conditions

1. Oligometastatic Lung Adenocarcinoma

Interventions

1. Drug: Erlotinib
2. Other: Local Therapies

MeSH:Adenocarcinoma of Lung

At least five patients will need to complete local therapy within 2 years of the study being open to accrual for the primary endpoint to be met.. Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A --- --- L861Q ---

- Any medical co-morbidities that would preclude surgery or radiation therapy Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A --- --- L861Q ---

The purpose of this study is to determine the safety, the antitumor activity and the pharmacokinetics of ASP8273 in EGFR tyrosine kinase inhibitor (EGFR-TKI)-naïve patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

NCT02500927

Conditions

1. EGFR-TKI-naïve Patients With NSCLC Harboring EGFR Activating Mutations

Interventions

1. Drug: ASP8273 Capsules
2. Drug: ASP8273 Capsules A

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Patients confirmed to have the deletion of exon 19 (del ex19), L858R, G719X, or L861Q mutation among the EGFR activating mutations (patients at the study site who are documented to have any of the above-stated EGFR activating mutations can be enrolled in the study). --- L858R --- --- L861Q ---

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Asia Pacific Patients with Locally Advanced/Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene

NCT02442349

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: AZD9291

MeSH:Lung Neoplasms Carcinoma, Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). --- L858R --- --- L861Q ---

Non-Small Cell Lung Cancer Lung Neoplasms Carcinoma, Carcinoma, Non-Small-Cell Lung This is a phase II, open label, single arm study assessing the safety and efficacy of AZD9291 (80 mg, orally, once daily) in Asia Pacific patients with a confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) sensitising mutation positive (ie, G719X, exon 19 deletion, L858R, L861Q) and T790M mutation positive (hereafter referred to as EGFRm+ and T790M+) un-resectable, locally advanced or metastatic NSCLC (Stage IIIB-IV), who have progressed on an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor(EGFR-TKI), either as first line treatment or following one line of EGFR-TKI and one line of platinum containing doublet chemotherapy. --- L858R --- --- L861Q ---

Alflutinib Mesylate Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation tumor cell in Xenograft mouse model. This study aims at local advanced or metastatic non-small cell lung cancer patients with T790M drug-resistant mutation.

NCT02973763

Conditions

1. NSCLC

Interventions

1. Drug: Alflutinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation) 5. Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy). --- L858R --- --- L861Q ---

The purpose of this study is to compare the frequency and abundance of T790M mutation among the different Clinical modes of EGFR-TKI failure.

NCT02418234

Conditions

1. Non-small Cell Lung Cancer Stage III
2. Non-Small-Cell Lung Cancer Metastatic

Interventions

1. Other: mutation detection
2. Other: ARMS and ddPCR
3. Genetic: ctDNA analysis

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Investigator confirmed progression according RECIST 1.1 during EGFR-TKI treatment within 28 days of the enrollment - Activating mutation (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) in the EGFR gene or have had at least partial response with EGFR TKI lasting ≥ 6 months - Patient must be able to comply with the protocol Exclusion Criteria: - Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined disease progression for more than 28 days while on previous EGFR-TKI treatment. --- G719A --- --- L858R --- --- L861Q ---

The purpose of this study is to try to improve the odds that your cancer may be cured. Pemetrexed and cisplatin are traditional chemotherapy drugs that have been shown to help some patients with non-small cell lung cancer. Many different types of cancer cells, including your type of lung cancer, have a protein on their surface called the epidermal growth factor receptor (EGFR). Stimulation of these receptors can result in growth of cancer cells and progression of cancer. In addition, your cancer has an EGFR mutation (a specific abnormality in the genetic code for EGFR). Erlotinib (TarcevaTM) is a newer drug which has shown benefit for patients with lung cancers that contain an EGFR mutation. Erlotinib works by blocking this receptor and depriving the cancer cells of this message to grow and multiply. In this research study, we plan to combine erlotinib with traditional chemotherapy drugs to see if the combination works better than chemotherapy alone. The main purpose of this research is to find out the good and bad effects that the combination of these 3 drugs (pemetrexed, cisplatin and erlotinib) has when given to patients with early stage non-small cell lung cancer before surgery. A secondary purpose is to find out the good and bad effects that occur when erlotinib is given to patients after surgery for 2 years.

NCT00577707

Conditions

1. Non Small Cell Lung Cancer
2. Lung Cancer

Interventions

1. Drug: erlotinib
2. Drug: Pemetrexed
3. Drug: Cisplatin
4. Procedure: Resection

MeSH:Lung Neoplasms

HPO:Neoplasm of the lung

Inclusion Criteria: - Pathologic confirmation of NSCLC - Patients must have previously untreated stage IB-IIIA NSCLC (T1-3N0-2M0) - Patients must have lung cancer with a documented EGFR activating mutation (exon 19 deletion, L858R, L861Q) - Patients must be candidates for resection with curative intent - Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded on CT) - Age greater or equal to 18 years - Karnofsky performance status greater or equal to 70% - Normal marrow function: leukocytes greater than or equal to 3,000/μl, absolute neutrophil count greater than or equal to 1,500/μl, platelets greater than or equal to 100,000/μl, hemoglobin greater than or equal to 9 gm/dl - Adequate renal function, with creatinine less than or equal to 1.3 mg/dl or calculated creatinine clearance greater to or equal to 60ml/min by Cockroft and Gault equation using parameters of age, weight (kg), and baseline serum creatinine (mg/dl) - Adequate hepatic function: Total bilirubin within normal limits, AST < 1.5 X UNL, alkaline phosphatase < 1.5 X UNL - Women of childbearing age must have a negative urine or blood pregnancy test - Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter - Patients must have ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Prior chemotherapy or radiation therapy, with the exception of chemotherapy for nononcologic conditions (ie, methotrexate for the treatment of rheumatoid arthritis) - Prior treatment with gefitinib, erlotinib, or other drugs that target EGFR - Patients must not be receiving any other investigational agents - Any evidence of interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded) - Patients who report a hearing deficit at baseline, even if it does not require a hearing aid or intervention, or interfere with activities of daily life (CTCAE grade 2 or higher) - Peripheral neuropathy > grade 1 - Known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study drugs. --- L858R --- --- L861Q ---

- Other serious illness or medical condition including unstable cardiac disease requiring treatment, history of significant neurologic or psychiatric disorders (including psychotic disorders, dementia, or seizures), or active uncontrolled infection - Women who are pregnant or breast-feeding - Psychiatric illness or social situation that would limit compliance with study requirements Inclusion Criteria: - Pathologic confirmation of NSCLC - Patients must have previously untreated stage IB-IIIA NSCLC (T1-3N0-2M0) - Patients must have lung cancer with a documented EGFR activating mutation (exon 19 deletion, L858R, L861Q) - Patients must be candidates for resection with curative intent - Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded on CT) - Age greater or equal to 18 years - Karnofsky performance status greater or equal to 70% - Normal marrow function: leukocytes greater than or equal to 3,000/μl, absolute neutrophil count greater than or equal to 1,500/μl, platelets greater than or equal to 100,000/μl, hemoglobin greater than or equal to 9 gm/dl - Adequate renal function, with creatinine less than or equal to 1.3 mg/dl or calculated creatinine clearance greater to or equal to 60ml/min by Cockroft and Gault equation using parameters of age, weight (kg), and baseline serum creatinine (mg/dl) - Adequate hepatic function: Total bilirubin within normal limits, AST < 1.5 X UNL, alkaline phosphatase < 1.5 X UNL - Women of childbearing age must have a negative urine or blood pregnancy test - Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter - Patients must have ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Prior chemotherapy or radiation therapy, with the exception of chemotherapy for nononcologic conditions (ie, methotrexate for the treatment of rheumatoid arthritis) - Prior treatment with gefitinib, erlotinib, or other drugs that target EGFR - Patients must not be receiving any other investigational agents - Any evidence of interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded) - Patients who report a hearing deficit at baseline, even if it does not require a hearing aid or intervention, or interfere with activities of daily life (CTCAE grade 2 or higher) - Peripheral neuropathy > grade 1 - Known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study drugs. --- L858R --- --- L861Q ---

Phase II trial to evaluate trametinib in patients with locally advanced non-squamous, non-small cell lung cancer (NSCLC) whose tumors harbor a non-synonymous NF-1 mutation, with progressive disease on at least one prior line of therapy.

NCT03232892

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Trametinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A --- --- S768I --- --- V769L --- --- T790M --- --- L833F --- --- L858R --- --- L861Q ---

The purpose of this study is to evaluate the efficacy and safety of olmutinib 600 mg QD in patients with T790M-positive non-small cell lung cancer (NSCLC) after treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI).

NCT04510415

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: Olmutinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- At least one documented EGFR mutation which is known to be related with susceptibility to EGFR-TKIs (including G719X, exon 19 deletion, L858R, and L861Q). --- L858R --- --- L861Q ---

The primary objective of this trial is to determine the maximum tolerated dose (MTD) and recommended Phase II doses for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib or gefitinib. Overall safety, pharmacokinetics and anti-tumor activity for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib, gefitinib or BIBW 2992 will be evaluated as secondary objectives. Initially a standard, 3+3 dose escalation will be performed to determine the MTD of BIBW 2992 when administered together with cetuximab in patients with advanced non small cell lung cancer and acquired resistance to erlotinib or gefitinib. Subsequently, the preliminary efficacy and safety of the identified MTD of cetuximab administered with BIBW 2992 will be explored in a combo arm via a further expansion of MTD cohort up to a total of 140 EGFR mutation positive NSCLC with acquired resistance to erlotinib/gefitinib. Furthermore, the safety and preliminary anti-tumor activity of the combination therapy in EGFR mutant NSCLC patients who developed acquired resistance (AR) to BIBW 2992, will be assessed in a sequential arm. The sequential arm will use a two-stage design with an early stopping rule after 12 patients with acquired resistance to BIBW 2992 have received up to 5 courses of BIBW 2992 plus cetuximab. If no responses are seen in 12 patients during 5 courses of combination therapy, accrual in the sequential arm will stop. If 1 or more responses are observed, the sequential arm will expand up to about 40 patients.

NCT01090011

Conditions

1. Carcinoma, Non-Small-Cell Lung

Interventions

1. Drug: Cetuximab
2. Drug: Cetuximab
3. Drug: BIBW 2992
4. Drug: BIBW 2992

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Progression-Free Survival was defined as the duration of time from start of treatment until the day of objective tumour progression confirmed by tumour imaging (PD according to RECIST 1.1) or death.. Inclusion criteria: 1. Pathologically or cytologically confirmed Stage IIIB/IV non-small cell lung cancer or recurrent disease following locoregional treatment 2. Either or both of the following: 1) A tumor which harbors an Epidermal Growth Factor Receptor (EGFR) -mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) from previous tumor biopsy or surgery. --- L858R --- --- L861Q ---

Women of childbearing potential (WOCBP), or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial; pregnancy or breast-feeding Inclusion criteria: 1. Pathologically or cytologically confirmed Stage IIIB/IV non-small cell lung cancer or recurrent disease following locoregional treatment 2. Either or both of the following: 1) A tumor which harbors an Epidermal Growth Factor Receptor (EGFR) -mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) from previous tumor biopsy or surgery. --- L858R --- --- L861Q ---

A multi-centre observational, non-interventional study is to dynamically monitor the changes of circulating tumor DNA (ctDNA) in late stage NSCLC patients under Gefitinib treatment.

NCT02804100

Conditions

1. Carcinoma, Non-Small-Cell Lung
2. Bronchial Neoplasms
3. Carcinoma, Bronchogenic
4. Lung Diseases
5. Lung Neoplasms

MeSH:Carcinoma Neoplasms Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Lung Diseases

HPO:Abnormal lung morphology Bronchial neoplasm Carcinoma Neoplasm Neoplasm of the lung Non-small cell lung carcinoma

- Activating EGFR mutations (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) - Able to comply with the required protocol and followed-up procedures, and able to receive oral medications Exclusion Criteria: - Histologically confirmed small cell lung cancer or other metastatic tumors - Patient had received prior chemotherapy or EGFR-TKIs treatment - Patients who harbor Exon20 T790M mutation Inclusion Criteria: - Provision of informed consent - Histologically confirmed stage IIIB/IV NSCLC. --- G719A --- --- L858R --- --- L861Q ---

- Activating EGFR mutations (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) - Able to comply with the required protocol and followed-up procedures, and able to receive oral medications Exclusion Criteria: - Histologically confirmed small cell lung cancer or other metastatic tumors - Patient had received prior chemotherapy or EGFR-TKIs treatment - Patients who harbor Exon20 T790M mutation Carcinoma, Non-Small-Cell Lung Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Lung Neoplasms Carcinoma Neoplasms Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Lung Diseases null --- G719A --- --- L858R --- --- L861Q ---

This is a study for patients with advanced non-small cell lung cancer with changes to their cancer cells called EGFR mutations. Mutated EGFR is important in the growth of cancer cells. Medical studies have shown that patients with EGFR mutation-positive lung cancer gain more benefit from targeted therapy drugs such as EGFR inhibitors than with standard chemotherapy. However, a significant proportion of patients carrying these sensitizing mutations do not respond well to the first-generation EGFR-TKIs (erlotinib and gefitinib), indicating the existence of intrinsic resistance mechanisms. Moreover, despite initial response to EGFR-TKIs, acquired resistance is inevitable in all patients. The investigators have recently shown that Cripto-1 overexpression in EGFR mutant NSCLC contributes to the intrinsic resistance to EGFR-TKIs through activation of the SRC oncogene. They have also shown that a combination of an EGFR-TKI (both erlotinib and osimertinib) and a Src inhibitor are synergistic in Cripto-1 overexpressing tumors in the laboratory. This study will be testing a combination of two drugs, dasatinib and osimertinib, to overcome resistance to EGFR-TKIs. Osimertinib (AZD9291) is a third-generation EGFR-TKI, which selectively blocks the activity of EGFR mutants, but spares that of wild type. The advantage of using osimertinib is that it inhibits not only the sensitizing EGFR mutations, but also the T790M mutant, which is the most common mechanism of acquired resistance. Dasatinib is a potent, orally available ABL1/SRC TKI, approved for the treatment of chronic myeloid leukemia (CML) in first-line and in patients with imatinib-resistant disease or intolerant, and is being actively studied in patients with advanced solid tumors. The first part of the study will involve finding the highest dose of dasatinib that can be given with osimertinib without causing severe side effects, finding out the side effects seen by giving dasatinib at different dose levels with osimertinib, and measuring the levels of dasatinib and osimertinib in blood at different dose levels. The second part will determine the effects of the combination of dasatinib and osimertinib and determine if the amount of Cripto-1 protein in your tumor or blood makes you more likely to have a good response to the combination of dasatinib and osimertinib.

NCT02954523

Conditions

1. EGFR Gene Mutation
2. Nonsmall Cell Lung Cancer

Interventions

1. Drug: Dasatinib
2. Drug: Osimertinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Presence of sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q). --- L858R --- --- L861Q ---

This is a single center and exploratory study, aiming to analyze the efficacy and safety of dacomitinib-a pan-HER and irreversible TKI in subjects with diagnosed stage IIIB/IV or recurrent NSCLC. All subjects will have tumors that test positive for at least one uncommon EGFR activating mutation (do not have drug-resistant pattern, e.g. 20 insertion or 20T790M). All patients will be of histo- and/or cytopathology confirmed. Determination of the EGFR mutation type will be performed in the pathological department of Shanghai Chest Hospital. Both ARMS method or targeted sequencing are acceptable. It is not acceptable for subjects with the presence of the exon 20T790M mutation or insertion together with either EGFR activating mutations (exon 19 deletion or the L858R mutation in exon 21) or uncommon EGFR mutations. 10ml peripheral blood must be available for concomitant study. All eligible subjects must have adequate renal, hepatic, and hematologic function, as defined in "inclusion criteria". Patients will receive continuous oral therapy with the study drugs (dacomitinib 45 mg) until progressive disease as defined by RECIST version 1.1 or judged by investigator that the patient no longer derives clinical benefit from study treatment. At the time of progression and removal from study treatment, the subject may receive any regulatory approved therapy at the judgment of the investigator. Timely and complete disease assessments in this study are important. Every effort should be made to ensure disease assessments performed as scheduled to prevent the introduction of bias into the assessment of efficacy. Failure to perform any of the required disease assessments will result in the inability to determine disease status for that time point. Frequent off schedule or incomplete disease assessments have the potential to weaken the study conclusion. Subjects who have progressive disease per RECIST version 1.1 confirmed by the investigator believes it is in their best interest to continue on their study therapy, will be allowed to continue on their therapy with or without local therapy (e.g. surgical removal and/or radiation of a single lesion), at the discretion of the investigator until any alternate or additional systemic anti-cancer therapy regimen is implemented. The subsequent new cancer therapy (including, for systemic therapy, drugs administered, date of initiation and discontinuation of each drug) and OS will be recorded. Each subject will be followed for survival status and subsequent cancer therapies up to 48 months from the date of first dosing. This data may be collected from subjects by telephone, and if collected should be entered into the CRF.

NCT04504071

Conditions

1. Non-small Cell Lung Cancer Metastatic
2. EGF-R Positive Non-Small Cell Lung Cancer

Interventions

1. Drug: Dacomitinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Mutation in exon 20: Including S768I, V765A, T783A, V774A, S784P, R776C, R776H, V765M, G779C, G779F, G779S, T783A, T783I, L798F, L798H, K806E, Q812R, L814P Mutation in exon 21: L861Q, R831H, V834I, L838P, L861R. --- S768I --- --- V765A --- --- T783A --- --- V774A --- --- S784P --- --- R776C --- --- R776H --- --- V765M --- --- G779C --- --- G779F --- --- G779S --- --- T783A --- --- T783I --- --- L798F --- --- L798H --- --- K806E --- --- Q812R --- --- L814P --- --- L861Q ---

The purpose of this study is to evaluate the efficacy of Olmutinib(Olita®) in patients with T790M-positive non-small cell lung cancer (NSCLC) confirmed using DNA extracted from extracellular vesicles of bronchoalveolar lavage fluid.

NCT03228277

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: Olmutinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

4. Confirmation that the tumor harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. Eastern Cooperative Oncology Group performance status of 0 to 2 6. --- L858R --- --- L861Q ---

To evaluate the safety, efficacy and immunogenicity of SCT510 combined with paclitaxel and carboplatin compared with bevacizumab combined with paclitaxel and carboplatin in the first-line treatment of locally advanced metastatic or recurrent squamous cell non-small cell lung cancer.

NCT03792074

Conditions

1. Non-squamous Cell Non-small Cell Lung Cancer

Interventions

1. Drug: SCT510
2. Drug: Bevacizumab
3. Drug: Paclitaxel
4. Drug: Carboplatin

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

21 (L858R, L861Q)) and ALK fusion.Subjects who have not previously undergone EGFR and ALK gene testing will need to undergo genetic testing during the screening period.Among them, subjects whose EGFR or ALK gene status cannot be determined for various reasons can be enrolled;Subjects who are known to have EGFR sensitive mutations and/or ALK fusion may also be enrolled if they are currently unable to obtain the corresponding targeted drugs (including the rejection of the subjects) and chemotherapy is standard treatment at the research center; 5. --- L858R --- --- L861Q ---

In recent years, with the progress in the treatment field, Non-Small Cell Lung Cancer(NSCLC) has become the most successful cancer species in precision medicine. Patients with positive driving genes such as EGFR, ALK, ROS1, BRAF and so on have clearly targeted drugs, which bring survival benefits to patients.However, about 50% of patients still lack a clear driving gene target, which has become the focus of current research.In the field of wild-type NSCLC with negative driver genes, the classic first-line treatment regimen is the two-drug regimen containing platinum.The study by Kimura T in the first-line treatment of 54 wild-type advanced NSCLC patients with carboplatin and pemetrexed showed that the ORR, mPFS and mOS of patients with wild-type non-squamous NSCLC treated with carboplatin permetrexine were 35.8%, 5.4 months and 12.7 months respectively. Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development.In the phase Ⅲ study, patients who failed at least two kinds of systemic chemotherapy (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 5.37 months and 9.46 months, the placebo group PFS and OS were 1.4 months and 6.37 months. The efficacy and safety of Anlotinib combined with Pemetrexed and Carboplatin followed by maintenance therapy with Anlotinib plus Pemetrexed as the first-line treatment in patients with advanced nonsquamous NSCLC deserve further exploration.

NCT03790228

Conditions

1. Non-squamous Cell Non-Small Cell Lung Cancer

Interventions

1. Drug: Anlotinib Combined With Pemetrexed And Carboplatin

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Exclusion Criteria: - Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer),Lung sarcomatoid carcinoma; - Had histologically confirmed lung squamous cell carcinoma, or adenosquamous carcinoma; - Patients with pathological fracture in bone metastasis of non-small-cell lung cancer; - Tumor histology or cytology confirmed EGFR mutagenesis [EGFR sensitive mutations include 18 exon point mutations (G719X), 19 exon deletions, 20 exon S768I mutations and 21 exon point mutations (L858R and L861Q)] and ALK gene rearrangement positivity, include EGFR/ALK status cannot be determined for various reasons; - Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor; - Medical history and combined history： 1. Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 28 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms and metastases in midbrain, pons, cerebellum, medulla oblongata, or spinal cord, brain metastases and local radiotherapy after two weeks to allow group); 2. The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks; 3. Had malignant tumors except NSCLC within 5 years before enrollment(except for patients with cervical carcinoma in situ , basal cell or squamous cell skin cancer who have undergone a curative treatment, local prostate cancer after radical resection, ductal carcinoma in situ or papillary thyroid cancer after radical resection); 4. Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;Note: Under the premise of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or low-dose aspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes; 5. Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g; 6. --- S768I --- --- L858R --- --- L861Q ---

Anlotinib which has shown an affirmatory efficacy in ALTER0303 controlled trial as a 3rd-line treatment on advanced NSCLC is a tyrosine kinase inhibitor with a favorable safety profile in phase I trial which mainly targets VEGFR1/2/3, FGFR, PDGFR and c-kit. The purpose of this trail is to establish whether advanced non-squamous NSCLC patients could benefit from the combination treatment of docetaxel, carboplatin and anlotinib as the first-line and maintenance treatment.

NCT03799601

Conditions

1. NSCLC

Interventions

1. Drug: Anlotinib
2. Drug: Docetaxel
3. Drug: Carboplatin

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Exclusion Criteria: - Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer), Lung sarcomatoid carcinoma; - Had histologically confirmed lung squamous cell carcinoma, or adenosquamous carcinoma; - Patients with pathological fracture in bone metastasis induced by non-small-cell lung cancer; - Tumor histology or cytology confirmed EGFR mutagenesis [EGFR sensitive mutations include 18 exon point mutations (G719X), 19 exon deletions, 20 exon S768I mutations and 21 exon point mutations (L858R and L861Q)] and ALK gene rearrangement positivity, include EGFR/ALK status cannot be determined for various reasons; - Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor; Medical history and combined history： - Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 28 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms and metastases in midbrain, pons, cerebellum, medulla oblongata, or spinal cord, brain metastases and local radiotherapy after two weeks to allow group); - The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks; - Had malignant tumors except NSCLC within 5 years before enrollment(except for patients with carcinoma in situ of the cervix , basal cell or squamous cell skin cancer who have undergone a curative treatment, local prostate cancer after radical resection, ductal carcinoma in situ or papillary thyroid cancer after radical resection); - Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy; Note: Under the condition of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or low-dose aspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes; - Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g; - The effects of surgery or trauma have been eliminated for less than 14 days before enrollment in subjects who have undergone major surgery or have severe trauma; - Severe acute or chronic infections requiring systemic treatment; Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) <50%; - There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for trauma; - Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment; Long-term unhealed wounds or fractures; - Decompensated diabetes or other ailments treated with high doses of glucocorticoids; - Factors that have a significant impact on oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction; - Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis; - Events of venous/venous thrombosis occurring within the first 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; - Physical examination and laboratory findings: 1. --- S768I --- --- L858R --- --- L861Q ---

Treatment of non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutation is mainly based on tyrosine kinase inhibitors (TKIs) targeting EGFR. 1st or 2nd generation inhibitors have been shown to be superior to chemotherapy in terms of Progression-Free Survival (PFS) when used as 1st line treatment. In case of progression at several metastatic sites, systemic treatment will be considered and will depend on the presence of the TKI resistance mutation, the T790M mutation. In the presence of the T790M mutation, osimertinib is superior to chemotherapy in terms of progression-free survival, while in the absence of the T790M mutation, platinum salt chemotherapy is recommended. In case of local progression, treatment of the site in progression by radiotherapy and/or surgery is considered. As these local treatments can cause long-term adverse effects, systemic treatments are increasingly being considered in this indication. Brain and leptomeningeal metastases are the most frequent isolated site of progression in EGFR mutated patients treated with TKI. The high frequency of isolated cerebral and leptomeningeal progression is a consequence of the lower diffusion of 1st and 2nd generation TKIs in the central nervous system (CNS). Osimertinib is a 3rd generation TKI that has the particularity of overcoming the T790M mutation and having greater brain penetration than 1st or 2nd generation TKIs, which could make it an attractive therapeutic option in the event of brain progression or leptomeningeal progression. However, its efficacy in patients with cerebral or leptomeningeal metastases is still poorly understood.

NCT04233021

Conditions

1. Non Small Cell Lung Cancer Metastatic
2. Leptomeningeal Metastasis
3. Brain Metastases
4. EGFR Activating Mutation

Interventions

1. Drug: Osimertinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis Neoplasms, Second Primary Meningeal Carcinomatosis

HPO:Neoplasm of the lung Non-small cell lung carcinoma

The following mutations are considered to be activating: L858R, exon 19 deletions, exon 19 insertions, L861Q, G719X. --- L858R --- --- L861Q ---

This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent. Part A will assess the effect of rifampicin on the pharmacokinetic (PK) parameters of AZD9291 and metabolites AZ5104 and AZ7550 following multiple oral dosing of both rifampicin and AZD9291 in a fasted state. Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients who complete Part A will be able to enter part B, and continue to receive AZD9291 80 mg once daily until: disease progression; they are no longer deriving clinical benefit; or any other reason.

NCT02197247

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Procedure: Pharmacokinetic sampling - AZD9291
2. Drug: Rifampicin
3. Drug: AZD9291 tablet dosing
4. Procedure: Pharmacokinetic sampling - rifampicin
5. Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks (Appendix G). 6. Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening. --- L858R --- --- L861Q ---

This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent. Part A will assess the effect of AZD9291 on the pharmacokinetic (PK) parameters of simvastatin and simvastatin acid, following multiple oral dosing of AZD9291 in a fasted state. Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients from Part A who completed treatment may continue to receive AZD9291 80 mg once daily until: disease progression; they are no longer deriving clinical benefit; or any other reason.

NCT02197234

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Procedure: Pharmacokinetic sampling - AZD9291
2. Drug: Simvastatin
3. Drug: AZD9291 tablet dosing
4. Procedure: Pharmacokinetic sampling - simvastatin
5. Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks (Appendix G). 6. Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening. --- L858R --- --- L861Q ---

Purpose of the study is to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. - the safety and tolerability of ASP8273. - the pharmacokinetics (PK) of ASP8273. - the antitumor activity of ASP8273.

NCT02192697

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: ASP8273

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Patients confirmed to have the del ex19, L858R, G719X, or L861Q mutation among the EGFR activating mutations (patients at the study site who are documented to have any of the above-stated EGFR activating mutations can be enrolled in the study). --- L858R --- --- L861Q ---

This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent. Part A will assess the effect of AZD9291 on the pharmacokinetic (PK) parameters of rosuvastatin, following multiple oral dosing of AZD9291 in the fasted state. Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients from Part A who completed treatment may continue to receive AZD9291 80 mg once daily as a single agent until: disease progression; they are no longer deriving clinical benefit; or any other reason.

NCT02317016

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Procedure: Pharmacokinetic sampling - AZD9291
2. Drug: AZD9291 tablet dosing
3. Drug: Rosuvastatin
4. Procedure: Pharmacokinetic sampling - rosuvastatin
5. Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks (Appendix G). 6. Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening. --- L858R --- --- L861Q ---

This phase I trial studies the side effects and best dose of c-Met inhibitor INCB028060 and erlotinib hydrochloride when given together in treating patients with previously treated non-small cell lung cancer. C-Met inhibitor INCB028060 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT01911507

Conditions

1. Recurrent Non-small Cell Lung Cancer

Interventions

1. Drug: INC280
2. Drug: erlotinib hydrochloride

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

G719X, exon 19 deletion, L858R, L861Q) - Systemic progression of disease (Response Evaluation Criteria in Solid Tumors [RECIST] or World Health Organization [WHO]) while on continuous treatment with gefitinib or erlotinib - Patients must have measurable disease; disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy - Failed 1-2 prior chemotherapies for advanced disease; prior erlotinib is allowed in the dose finding phase and expansion cohort A (Patients in expansion cohort B must be erlotinib naïve and have v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KRAS] wild type tumor) - Patients must be willing to be off therapy for a minimum of two weeks (In expansion cohort A patients on erlotinib do not have to discontinue treatment) - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Life expectancy greater than 3 months - Hemoglobin > 9 g/dL (International System [SI] units: 90 g/L) without transfusion support or growth factors within 10 days of starting INC280 - Platelet count >= 75 x 10^9/L - Absolute neutrophil count (ANC) >= 1.2 x 10^9/L without growth factor support - Total bilirubin =< 2 x upper limit of normal (ULN) - Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) - Serum creatinine =< 2 x ULN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting serum triglyceride level =< 500 mg/dL Exclusion Criteria: - Patients who have had major surgery within 4 weeks of initiation of study medication, excluding the placement of vascular access - Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data - Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia - Severely impaired lung function - Active (acute or chronic) or uncontrolled infection - Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy - Liver disease (i.e. --- L858R --- --- L861Q ---

ASK120067 Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation tumor cell in Xenograft mouse model. This study aims at local advanced or metastatic non-small cell lung cancer patients with T790M drug-resistant mutation.

NCT03502850

Conditions

1. Locally Advanced or Metastatic NSCLC

Interventions

1. Drug: ASK120067

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Inclusion Criteria: - Patients of either gender, aged from 18 years older to 70. - Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC - Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation) - Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. --- L858R --- --- L861Q ---

- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements Inclusion Criteria: - Patients of either gender, aged from 18 years older to 70. - Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC - Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation) - Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. --- L858R --- --- L861Q ---

This is a Phase 1/2, open-label, multicenter, sequential dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of ZN-e4 administered orally in subjects with advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations who have progressed while on treatment with an EGFR tyrosine kinase inhibitor (TKI) agent (other lines of treatment are allowed, except for other epidermal growth factor receptor inhibitors [EGFRis]) for Phase 1; and for Phase 2, subjects who have T790M+ and are osimertinib naïve (Cohort 1), and also those who have not been treated with an EGFR Inhibitor (EGFRi) (Cohort2).

NCT03446417

Conditions

1. Carcinoma, Non-Small-Cell Lung

Interventions

1. Drug: ZN-e4

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- Phase 1 only: Confirmation that the tumor harbors an EGFR mutation known to be associated with aberrations that are amenable to EGFRi therapy including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q. --- L858R --- --- L861Q ---

- Measurable disease meeting the criteria specified by RECIST v1.1 - Phase 2, Cohort 1 only: Subjects must have confirmation of tumor T790M mutation status (confirmed positive) and are osimertinib naïve - Phase 2, Cohort 2 only: EGFR aberrations that are amenable to EGFRi therapy, including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q, and be EGFRi naïve EXCLUSION CRITERIA - Subjects who have received only neoadjuvant or adjuvant therapy for NSCLC. --- T790M --- --- L858R --- --- L861Q ---

This is one randomized, double-blind, placebo-controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with standard 1st-line chemotherapy in treatment-naïve advanced non-small cell lung cancer (NSCLC); and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population. About 450 subjects with advanced non-small cell lung cancer without activated EGFR mutation (exon 19 deletion, or exon 21 L858R, exon 21 L861Q, exon 18 G719X or exon 20 S768I mutations) and ALK fusion will be 2:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. The stratification will be based on the following factors: PD-L1 expression (TC≥1% vs TC<1%); Smoking state (often smoking vs no smoking or infrequent smoking); Pathological type (squamous cell carcinoma vs non-squamous cell carcinoma).

NCT03856411

Conditions

1. Treatment-naive Advanced Non-small Cell Lung Cancer

Interventions

1. Drug: TORIPALIMAB INJECTION (JS001 ) combine with chemotherapy

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

About 450 subjects with advanced non-small cell lung cancer without activated EGFR mutation (exon 19 deletion, or exon 21 L858R, exon 21 L861Q, exon 18 G719X or exon 20 S768I mutations) and ALK fusion will be 2:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. --- L858R --- --- L861Q ---

This is a phase I/Ib, open-label, single-center, single-arm study of alisertib and osimertinib for patients with stage IV EGFR-mutated lung cancer, incorporating both a dose escalation and dose-expansion phase

NCT04085315

Conditions

1. Lung C
2. Lung Cancer Metastatic
3. EGFR Gene Mutation

Interventions

1. Drug: Osimertinib
2. Drug: Alisertib

MeSH:Lung Neoplasms

HPO:Neoplasm of the lung

2. Male or female patients ≥18 years of age 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix 1). 4. Documented activating EGFR mutation (Exon 19 deletion, Exon 19 insertion, E709K, G719X, S768I, V769L, T790M, L833F, L833V, V834L, H835L, L858R, A859S, K860I, L861Q, A871E, V843I, or H870R) on tumor sample or cell-free DNA sample performed in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory. 5. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. --- E709K --- --- S768I --- --- V769L --- --- T790M --- --- L833F --- --- L833V --- --- V834L --- --- H835L --- --- L858R --- --- A859S --- --- K860I --- --- L861Q ---

This partially randomized phase II trial studies how well nivolumab, cabozantinib s-malate, and ipilimumab work in treating patients with stage IV non-small cell lung cancer that has come back. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nivolumab, cabozantinib s-malate, and ipilimumab may work better than cabozantinib s-malate alone in treating patients with stage IV non-small cell lung cancer.

NCT03468985

Conditions

1. Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
2. Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
3. Stage IV Lung Non-Small Cell Cancer AJCC v7

Interventions

1. Drug: Cabozantinib
2. Drug: Cabozantinib S-malate
3. Biological: Ipilimumab
4. Other: Laboratory Biomarker Analysis
5. Biological: Nivolumab
6. Other: Questionnaire Administration

MeSH:Carcinoma Carcinoma, Non-Small-Cell Lung

HPO:Carcinoma Non-small cell lung carcinoma

Data collected from the tobacco use assessment in each parent study will not be analyzed and reported in the clinical study report.. Inclusion Criteria: - ELIGIBILITY CRITERIA FOR STEP 0 - Patients with tumors with the following molecular alterations must submit testing results via Medidata Rave to determine eligibility to Arm T; the study chair, co-chair, biology co-chair, or a delegate must review the molecular testing and agree that the testing meets one of the molecular eligibility criteria below: - ROS1 gene rearrangement by fluorescence in situ hybridization (FISH) or deoxyribonucleic acid (DNA) analysis (may have progressed on prior crizotinib therapy) - MET exon 14 splice mutations on DNA analysis (may have progressed on prior crizotinib therapy) - MET high amplification by FISH or DNA analysis or other MET mutations predicted to be sensitive to MET inhibitor (no prior targeted therapy allowed) - RET gene rearrangement by FISH or DNA analysis (no prior targeted therapy allowed) - Institutions will be notified of the patient's eligibility status for Arm T within two (2) business days of submission of the molecular testing reports - If patients do not have tumors with the above molecular alterations noted proceed directly to step 1 - ELIGIBILITY CRITERIA FOR STEP 1 - For patients with known molecular alterations, institution has been notified that patient is deemed eligible for Arm T per review of molecular testing reports - Pathologically confirmed non-squamous non-small cell lung carcinoma (NSCLC) - Stage IV disease (includes M1a, M1b, or recurrent disease), according to the 7th edition of the lung cancer tumor, node, and metastasis (TNM) classification system - Predominant non-squamous histology (patients with NSCLC not otherwise specified [NOS] are eligible); mixed tumors will be categorized by the predominant cell type; if small cell elements are present the patient is ineligible - Tumors must be tested and known negative for EGFR tyrosine kinase inhibitor (TKI) sensitizing mutations (EGFR exon 19 deletions, L858R, L861Q, G719X) and ALK gene rearrangements by routine Clinical Laboratory Improvement Act (CLIA)-certified clinical testing methods; negative circulating tumor DNA results alone are not acceptable; prior testing for tumor PD-L1 status is not required - Patients must have progressed radiographically following first line platinum-based chemotherapy, no additional lines of therapy are permitted - NOTE: Prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy - Exception for targeted therapy sub-study (Arm T): At least one line of prior chemotherapy or targeted therapy is required, but there is no limit on number of prior treatments - Patients must have measurable disease as defined by RECIST v. 1.1 criteria; baseline measurements and evaluation of ALL sites of disease must be obtained within 4 weeks prior to registration - No prior anti-MET therapy such as crizotinib or cabozantinib, or PD-1/PD-L1 immune checkpoint inhibitor therapy (such as nivolumab, pembrolizumab, atezolizumab) or CTLA4 inhibitor therapy (such as ipilimumab); no prior allergic reaction to small molecule tyrosine kinase inhibitors or monoclonal antibodies - Exception for targeted therapy sub-study (Arm T): Prior crizotinib may be allowed depending on the gene alteration - Any prior chemotherapy (based on administration schedule) must have been completed in greater than or equal to the following times prior to registration: - Chemotherapy/ targeted oral therapy administered in a daily or weekly schedule must be completed >= 1 week prior to registration; - Any chemotherapy administered in an every 2 week or greater schedule must be completed >= 2 weeks prior to registration - Additionally, patients should be recovered to equal to or less than grade 1 toxicities related to any prior treatment, unless adverse event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy - No prior radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks prior to registration - Patients with no known brain metastasis must have baseline brain imaging within 12 weeks prior to study registration not demonstrating brain metastases OR - Patients with known brain metastases must have baseline brain imaging within 4 weeks prior to study registration and meet all of the following criteria: - Have completed treatment to all symptomatic brain metastases (with whole brain radiation or radiosurgery) >= 4 weeks prior to registration, or have undergone complete neurosurgical resection >= 3 months prior to registration - Be clinically stable from brain metastases at time of screening, if no treatment was administered - Known leptomeningeal disease is not allowed - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - NOTE: Participants with impaired decision-making capacity (IDMC) should not be allowed to participate in this study due to its complexity - Patients must have anticipated life expectancy greater than 3 months - Absolute neutrophil count >= 1,500/mm^3 (within 2 weeks prior to registration) - Platelets >= 100,000/mm^3 (within 2 weeks prior to registration) - Hemoglobin >= 9 g/dL (within 2 weeks prior to registration) - Subject has prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) test =< 1.3 x the laboratory upper limit of normal (ULN) (within 2 weeks prior to registration) - Total bilirubin =< 1.5 x ULN (within 2 weeks prior to registration) - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN (within 2 weeks prior to registration) - Serum albumin >= 2.8 g/dL (within 2 weeks prior to registration) - Serum calcium (absolute or albumin corrected), magnesium and potassium >= lower limit of normal (LLN) (within 2 weeks prior to registration) - NOTE: serum calcium, magnesium and potassium can be replaced if values are below LLN - Creatinine =< 1.5 x ULN or calculated (Cockcroft-Gault formula) or measured creatinine clearance >= 50 mL/min/1.73 --- L858R --- --- L861Q ---

- Serious non-healing wound/ulcer/bone fracture within 28 days prior to registration - History of organ transplant - Concurrent symptomatic untreated hypothyroidism within 7 days prior to registration - History of surgery as follows: - Major surgery (as an example, surgery requiring anesthesia and a > 24 hour hospital stay) within 3 months prior to registration, with wound healing at least 28 days prior to registration - Minor surgery within 28 days prior to registration with complete wound healing at least 10 days prior to registration - Minor procedures within 7 days prior to registration such as thoracentesis, paracentesis, or 18 g or smaller needle biopsy of tumor - Patients with clinically relevant ongoing complications from prior surgery are not eligible - Patients must have corrected QT interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before registration - Patients must be able to swallow tablets - No currently active other malignancies which require systemic treatment - No patients that have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted - No patients with known active autoimmune disease or known history of autoimmune disease for which recurrence may affect vital organ function or require immune suppressive treatment including systemic corticosteroids; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, autoimmune hepatitis; patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease; patients with vitiligo, endocrine deficiencies including type I diabetes mellitus or thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible - No ongoing major illness or psychosocial issues that would limit compliance with the protocol - Women must not be pregnant or breast-feeding due to contraindications with the study agents - All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy - A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) - Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP must use an accepted and effective method of contraception or abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment for women of childbearing potential and 7 months after the last dose of protocol treatment for males who are sexually active with WOCBP - Patients with known human immunodeficiency virus (HIV) disease taking antiretroviral therapy are excluded because there are no safety data with the combination of antiretroviral therapy and cabozantinib or ipilimumab or nivolumab with ipilimumab - Patients with known chronic active hepatitis B (defined as a positive hepatitis B surface antigen and/or hepatitis B viral load in the last Inclusion Criteria: - ELIGIBILITY CRITERIA FOR STEP 0 - Patients with tumors with the following molecular alterations must submit testing results via Medidata Rave to determine eligibility to Arm T; the study chair, co-chair, biology co-chair, or a delegate must review the molecular testing and agree that the testing meets one of the molecular eligibility criteria below: - ROS1 gene rearrangement by fluorescence in situ hybridization (FISH) or deoxyribonucleic acid (DNA) analysis (may have progressed on prior crizotinib therapy) - MET exon 14 splice mutations on DNA analysis (may have progressed on prior crizotinib therapy) - MET high amplification by FISH or DNA analysis or other MET mutations predicted to be sensitive to MET inhibitor (no prior targeted therapy allowed) - RET gene rearrangement by FISH or DNA analysis (no prior targeted therapy allowed) - Institutions will be notified of the patient's eligibility status for Arm T within two (2) business days of submission of the molecular testing reports - If patients do not have tumors with the above molecular alterations noted proceed directly to step 1 - ELIGIBILITY CRITERIA FOR STEP 1 - For patients with known molecular alterations, institution has been notified that patient is deemed eligible for Arm T per review of molecular testing reports - Pathologically confirmed non-squamous non-small cell lung carcinoma (NSCLC) - Stage IV disease (includes M1a, M1b, or recurrent disease), according to the 7th edition of the lung cancer tumor, node, and metastasis (TNM) classification system - Predominant non-squamous histology (patients with NSCLC not otherwise specified [NOS] are eligible); mixed tumors will be categorized by the predominant cell type; if small cell elements are present the patient is ineligible - Tumors must be tested and known negative for EGFR tyrosine kinase inhibitor (TKI) sensitizing mutations (EGFR exon 19 deletions, L858R, L861Q, G719X) and ALK gene rearrangements by routine Clinical Laboratory Improvement Act (CLIA)-certified clinical testing methods; negative circulating tumor DNA results alone are not acceptable; prior testing for tumor PD-L1 status is not required - Patients must have progressed radiographically following first line platinum-based chemotherapy, no additional lines of therapy are permitted - NOTE: Prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy - Exception for targeted therapy sub-study (Arm T): At least one line of prior chemotherapy or targeted therapy is required, but there is no limit on number of prior treatments - Patients must have measurable disease as defined by RECIST v. 1.1 criteria; baseline measurements and evaluation of ALL sites of disease must be obtained within 4 weeks prior to registration - No prior anti-MET therapy such as crizotinib or cabozantinib, or PD-1/PD-L1 immune checkpoint inhibitor therapy (such as nivolumab, pembrolizumab, atezolizumab) or CTLA4 inhibitor therapy (such as ipilimumab); no prior allergic reaction to small molecule tyrosine kinase inhibitors or monoclonal antibodies - Exception for targeted therapy sub-study (Arm T): Prior crizotinib may be allowed depending on the gene alteration - Any prior chemotherapy (based on administration schedule) must have been completed in greater than or equal to the following times prior to registration: - Chemotherapy/ targeted oral therapy administered in a daily or weekly schedule must be completed >= 1 week prior to registration; - Any chemotherapy administered in an every 2 week or greater schedule must be completed >= 2 weeks prior to registration - Additionally, patients should be recovered to equal to or less than grade 1 toxicities related to any prior treatment, unless adverse event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy - No prior radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks prior to registration - Patients with no known brain metastasis must have baseline brain imaging within 12 weeks prior to study registration not demonstrating brain metastases OR - Patients with known brain metastases must have baseline brain imaging within 4 weeks prior to study registration and meet all of the following criteria: - Have completed treatment to all symptomatic brain metastases (with whole brain radiation or radiosurgery) >= 4 weeks prior to registration, or have undergone complete neurosurgical resection >= 3 months prior to registration - Be clinically stable from brain metastases at time of screening, if no treatment was administered - Known leptomeningeal disease is not allowed - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - NOTE: Participants with impaired decision-making capacity (IDMC) should not be allowed to participate in this study due to its complexity - Patients must have anticipated life expectancy greater than 3 months - Absolute neutrophil count >= 1,500/mm^3 (within 2 weeks prior to registration) - Platelets >= 100,000/mm^3 (within 2 weeks prior to registration) - Hemoglobin >= 9 g/dL (within 2 weeks prior to registration) - Subject has prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) test =< 1.3 x the laboratory upper limit of normal (ULN) (within 2 weeks prior to registration) - Total bilirubin =< 1.5 x ULN (within 2 weeks prior to registration) - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN (within 2 weeks prior to registration) - Serum albumin >= 2.8 g/dL (within 2 weeks prior to registration) - Serum calcium (absolute or albumin corrected), magnesium and potassium >= lower limit of normal (LLN) (within 2 weeks prior to registration) - NOTE: serum calcium, magnesium and potassium can be replaced if values are below LLN - Creatinine =< 1.5 x ULN or calculated (Cockcroft-Gault formula) or measured creatinine clearance >= 50 mL/min/1.73 --- L858R --- --- L861Q ---

This is an open-label, single centre, Phase I study to determine the brain exposure of [11C]osimertinib in patients with EGFRm NSCLC with brain metastases.

NCT03463525

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Osimertinib
2. Drug: [11C]osimertinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or T790M EGFR resistance mutation as assessed by local laboratory/or central laboratory via tissue/cytology or in plasma. --- L858R --- --- L861Q ---

The study is designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of EGF816 in combination with INC280 and to estimate the preliminary anti-tumor activity of EGF816 in combination with INC280 in patients with advanced non-small cell lung cancer (NSCLC) with documented EGFR mutation.

NCT02335944

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: INC280
2. Drug: EGF816

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

L861Q, G719X, S768I) - Presence of at least one measurable lesion according to RECIST v.1.1 - ECOG performance status ≤1 - Patients must be screened for HBV. --- L861Q ---

This is a Phase III, randomised, controlled, 3-arm, multi-centre study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with resectable EGFRm Non-Small Cell Lung Cancer

NCT04351555

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: Osimertinib
2. Drug: Cisplatin
3. Drug: Carboplatin
4. Drug: Placebo
5. Drug: Pemetrexed

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing - A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q). --- L858R --- --- T790M --- --- L861Q ---

This phase II trial compares cabozantinib alone and the combination of cabozantinib and nivolumab to standard chemotherapy in the treatment of patients with non-squamous non-small cell lung cancer (NSCLC). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ramucirumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as docetaxel, gemcitabine hydrochloride, paclitaxel, and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving cabozantinib alone or in combination with nivolumab may be more effective than standard chemotherapy in treating patients with non-small cell lung cancer.

NCT04310007

Conditions

1. Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
2. Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
3. Stage III Lung Cancer AJCC v8
4. Stage IIIA Lung Cancer AJCC v8
5. Stage IIIB Lung Cancer AJCC v8
6. Stage IIIC Lung Cancer AJCC v8
7. Stage IVA Lung Cancer AJCC v8
8. Unresectable Lung Non-Squamous Non-Small Cell Carcinoma

Interventions

1. Drug: Cabozantinib S-malate
2. Drug: Docetaxel
3. Drug: Gemcitabine Hydrochloride
4. Drug: Nab-paclitaxel
5. Biological: Nivolumab
6. Drug: Paclitaxel
7. Biological: Ramucirumab

MeSH:Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Carcinoma Neoplasm of the lung Non-small cell lung carcinoma

If small cell elements are present the patient is ineligible - ELIGIBILITY CRITERIA FOR STEP 0 (PRE-REGISTRATION): Patient's tumor(s) must be tested and known negative for EGFR tyrosinase kinase inhibitor (TKI) sensitizing mutations (EGFR Exon 19 deletions, L858R, L861Q, G719X) and ALK gene rearrangements (by fluorescence in situ hybridization [FISH], next generation sequencing [NGS], or immunohistochemistry [IHC]) by routine Clinical Laboratory Improvement Act (CLIA)-certified clinical testing methods. --- L858R --- --- L861Q ---

This is a research study to find out if a drug called, osimertinib, is safe and effective in treating advanced Non-Small Cell Lung Cancer (NSCLC) by targeting the treatment of epidermal growth factor receptor (EGFR) mutation exon 18 G719X, exon 20 S7681, or exon 21 L861Q. Patients on the study will not have had previous tyrosine kinase inhibitor (TKI) treatment.

NCT03434418

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: osimertinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

A Study Osimertinib in Patients With Stage 4 Non-small Cell Lung Cancer With Uncommon EGFR Mutations This is a research study to find out if a drug called, osimertinib, is safe and effective in treating advanced Non-Small Cell Lung Cancer (NSCLC) by targeting the treatment of epidermal growth factor receptor (EGFR) mutation exon 18 G719X, exon 20 S7681, or exon 21 L861Q. --- L861Q ---

Overall survival as noted by follow-up via composite of telephone or medical record review.. Overall survival as defined as time from starting study therapy until death from any causes.. Inclusion Criteria: - EGFR mutations as performed on a CLIA certified laboratory demonstrating EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q. --- S768I --- --- L861Q ---

- Grade ≥ 2 blurred vision, conjunctivitis, corneal ulcer, dry eye, or keratitis Inclusion Criteria: - EGFR mutations as performed on a CLIA certified laboratory demonstrating EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q. --- S768I --- --- L861Q ---

- Grade ≥ 2 blurred vision, conjunctivitis, corneal ulcer, dry eye, or keratitis Non Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung This is a research study to find out if a drug called, osimertinib, is safe and effective in treating advanced Non-Small Cell Lung Cancer (NSCLC) by targeting the treatment of epidermal growth factor receptor (EGFR) mutation exon 18 G719X, exon 20 S7681, or exon 21 L861Q. --- L861Q ---

Patients who have one of the following EGRF mutations: exon 18 G719X, exon 20 S7681, or exon 21 L861Q) may be eligible to participate in this study. --- L861Q ---

This phase I trial studies the side effects and best dose of WSD0922-FU for the treatment of glioblastoma, anaplastic astrocytoma, or non-small cell lung cancer that has spread to the central nervous system (central nervous system metastases). WSD0922-FU is a targeted treatment which blocks the EGFR protein - a strategy that has led to a lot of benefit in patients with many different cancers. WSD0922-FU may also be able to get into cancers in the brain and spinal cord and help patients with brain and spinal cord cancers.

NCT04197934

Conditions

1. Anaplastic Astrocytoma, IDH-Wildtype
2. Glioblastoma, IDH-Wildtype
3. Lung Non-Small Cell Carcinoma
4. Metastatic Malignant Neoplasm in the Central Nervous System
5. Metastatic Malignant Neoplasm in the Leptomeninges

Interventions

1. Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
2. Procedure: Therapeutic Conventional Surgery

MeSH:Neoplasms Glioblastoma Astrocytoma Neoplasms, Second Primary Carcinoma, Non-Small-Cell Lung

HPO:Astrocytoma Glioblastoma multiforme Neoplasm Non-small cell lung carcinoma Subependymal giant-cell astrocytoma

Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q ---

Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q --- --- L858R --- --- G719A --- --- L861Q ---

History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU - Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU - Inadequate bone marrow reserve or organ function - Patients with NSCLC LM who are unable to undergo collection of CSF Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q ---

History of hypersensitivity to active or inactive excipients of WSD0922-FU or drugs with a similar chemical structure or class to WSD0922-FU - Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU - Inadequate bone marrow reserve or organ function - Patients with NSCLC LM who are unable to undergo collection of CSF Inclusion Criteria: - Pre-Registration - Inclusion Criteria Specific to Dose Escalation Cohort - Histological confirmation of either glioblastoma, IDH wildtype (GBM), anaplastic astrocytoma, IDH wildtype (AA) or non-small cell lung cancer (NSCLC) - EGFR Status: - GBM/AA must have EGFR amplification and/or EGFRvIII mutation - NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Pre-Registration - Inclusion Criteria Specific to Dose Expansion Cohorts - Glioblastoma, IDH wildtype/Anaplastic astrocytoma, IDH wildtype (GBM/AA) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have EGFR amplification and/or EGFRvIII mutation - Brain Tumor Penetration (BTP) Cohort: - Diagnosis: Histological confirmation of either glioblastoma, IDH wildtype (GBM) or anaplastic astrocytoma, IDH wildtype (AA) - EGFR status: GBM/AA must have been previously demonstrated to have EGFR amplification and/or EGFRvIII mutation based on any prior resection - Non-Small Cell Lung Cancer Leptomeningeal Metastases (NSCLC LM) cohort: - Diagnosis: Histological confirmation of non-small cell lung cancer (NSCLC) - EGFR status: NSCLC must have confirmed activating EGFR mutation (including Del19, L858R, EGFRvIII, G719A, L861Q) - Registration -Inclusion Criteria Specific to Dose Escalation Cohort - Previous treatments: - Patients with GBM/AA must have been previously treated with radiation and temozolomide - Patients with NSCLC must have been previously treated with at least one line of single-agent therapy with an EGFR TKI e.g. --- L858R --- --- G719A --- --- L861Q --- --- L858R --- --- G719A --- --- L861Q ---

This is a Phase 1b, open-label, multicentre study of AZD6094 in combination with gefitinib in patients with epidermal growth factor receptor (EGFR) mutation positive (m+) and progressed on EGFR Tyrosine kinase inhibitor (TKI) treatment.

NCT02374645

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: Volitinib
2. Drug: gefitinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC patients who are harbouring an EGFR mutation known to be associated with EGFR-TKI sensitivity (including exon 19 deletion, L858R, L861Q, G719X). --- L858R --- --- L861Q ---

The aim of the study is to collect real world information on patients with locally advanced or metastatic non small cell lung cancer (NSCLC) who progressed after first line treatment with an approved Tyrosine-Kinase Inhibitor (TKI), who are known to be T790M positive and have been prescribed second line platinum-based chemotherapy (Pemetrexed + Cisplatin /Carboplatin).

NCT02368990

Conditions

1. Non Small Cell Lung Cancer

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- Confirmation prior to enrolment into the study that the tumour harbours the following EGFR mutations known to be associated with EGFR-targeted TKI sensitivity: Ex19Del, L858R, L861Q, and G719X. --- L858R --- --- L861Q ---

There are Epidermal Growth Factor Receptor (EGFR) mutations known to be associated with EGFR-targeted TKI sensitivity ( Ex19Del, L858R, L861Q, and G719X). --- L858R --- --- L861Q ---

This phase I/Ib trial studies the side effects and best dose of pembrolizumab when given together with afatinib dimaleate in treating patients with non-small cell lung cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment, or has come back and does not respond to erlotinib hydrochloride. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and afatinib dimaleate together may be an effective treatment for non-small cell lung cancer.

NCT02364609

Conditions

1. Recurrent Non-Small Cell Lung Carcinoma
2. Stage IIIA Non-Small Cell Lung Cancer
3. Stage IIIB Non-Small Cell Lung Cancer
4. Stage IV Non-Small Cell Lung Cancer

Interventions

1. Drug: Afatinib Dimaleate
2. Biological: Pembrolizumab

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Standard descriptive methods will be used to summarize the baseline levels and changes in baseline levels will allow to examine whether observed patterns are consistent with hypothesized patterns.. Inclusion Criteria: - Incurable, advanced or metastatic/recurrent non-small cell lung cancer with EGFR activating mutations (exon 19 del, exon 21 L858R, L861Q, G718X); who have radiologic and/or clinically progressive disease on erlotinib at any point during the patient's cancer treatment as determined by the Investigator - Be willing and able to provide written informed consent for the trial - Have a life expectancy of at least 3 months - Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Adequate archival tissue for determination of EGFR-mutation status and PD-L1 status with a leftover cell block (or equivalent) for additional immune correlates from a tumor lesion biopsied in the last 60 days that has not been previously irradiated occurring: 1) after progression on erlotinib and no intervening systemic treatment between biopsy and initiation of MK-3475 and afatinib or amenable to repeat biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance scale - Be willing to consent for biopsy at baseline (if inadequate archival tissue per inclusion criteria above) and an on treatment biopsy; have a tumor in a location that in the opinion of the investigator that is amenable to biopsy or have provided tissue for PD-L1 and other biomarker analysis from a newly obtained (within 60 days) formalin fixed tumor tissue from a recent biopsy of a tumor lesion not previously irradiated; no systemic antineoplastic therapy may be administered between the PD- L1 biopsy and initiating study medication; fine needle aspirates are not acceptable; needle or excisional biopsies, or resected tissue is required; the tissue sample must be received by the central vendor (Labcorp) and evaluated for adequacy prior to starting therapy - There is no limit to the number of prior treatments for this phase I trial - Absolute neutrophil count (ANC) >= 1,500/mcL - Platelets >= 100,000/mcL - Hemoglobin >= 9 g/dL or >= 5.6 mmol/L - Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 x upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN - Creatinine clearance should be calculated per institutional standard - Serum total bilirubin =< 1.5 x ULN - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR < 5 x ULN for subjects with liver metastases - International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants - Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required - Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year - Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Exclusion Criteria: - Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment - Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier; denosumab is allowed as long as not < 1 week prior to study day 1 and not administered on day of MK-3475 infusion - Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent - Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study - Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy - Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment - Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study - Has evidence of interstitial lung disease or active, non-infectious pneumonitis that required oral or intravenous glucocorticoids to assist with management; lymphangitic spread of the non-small cell lung cancer (NSCLC) is not exclusionary - Has an active infection requiring intravenous systemic therapy - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator - Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial - History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator; myocardial infarction within 6 months prior to enrollment - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment - Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) - Known hypersensitivity to afatinib or the excipients of any of the trial drugs - Prior participation in an afatinib clinical study, even if not assigned to afatinib treatment - Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) - Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) - Has received a live vaccine within 30 days prior to the first dose of trial treatment - The presence of poorly controlled gastrointestinal disorders that could affect the absorption of the afatinib (e.g. --- L858R --- --- L861Q ---

Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption) - Subjects that require treatment with a strong inhibitor of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) will be excluded; they may be included if there is an alternate treatment available (not a strong CYP3A4 inhibitor) and they are willing to switch prior to enrollment; if a subject opts to change from a strong CYP 3A4 inhibitor to a weaker CYP 3A4 inhibitor, the subject must stop the strong CYP 3A4 inhibitor 7 days before study drug administration - Receiving drugs known to be strong inducers or inhibitors of permeability (P)-glycoprotein that are known to interact with afatinib including, but not limited to: ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; the subject must stop the strong inducer or inhibitor of P-glycoprotein 7 days before or 5 half lives before study drug administration (whichever timepoint is longer) - Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study - Hormonal treatment within 2 weeks prior to start of study treatment - Radiotherapy within 4 weeks prior to enrollment, except as follows: - Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior to enrollment, and - Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor-investigator prior to enrolling - Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of study Inclusion Criteria: - Incurable, advanced or metastatic/recurrent non-small cell lung cancer with EGFR activating mutations (exon 19 del, exon 21 L858R, L861Q, G718X); who have radiologic and/or clinically progressive disease on erlotinib at any point during the patient's cancer treatment as determined by the Investigator - Be willing and able to provide written informed consent for the trial - Have a life expectancy of at least 3 months - Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Adequate archival tissue for determination of EGFR-mutation status and PD-L1 status with a leftover cell block (or equivalent) for additional immune correlates from a tumor lesion biopsied in the last 60 days that has not been previously irradiated occurring: 1) after progression on erlotinib and no intervening systemic treatment between biopsy and initiation of MK-3475 and afatinib or amenable to repeat biopsy - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance scale - Be willing to consent for biopsy at baseline (if inadequate archival tissue per inclusion criteria above) and an on treatment biopsy; have a tumor in a location that in the opinion of the investigator that is amenable to biopsy or have provided tissue for PD-L1 and other biomarker analysis from a newly obtained (within 60 days) formalin fixed tumor tissue from a recent biopsy of a tumor lesion not previously irradiated; no systemic antineoplastic therapy may be administered between the PD- L1 biopsy and initiating study medication; fine needle aspirates are not acceptable; needle or excisional biopsies, or resected tissue is required; the tissue sample must be received by the central vendor (Labcorp) and evaluated for adequacy prior to starting therapy - There is no limit to the number of prior treatments for this phase I trial - Absolute neutrophil count (ANC) >= 1,500/mcL - Platelets >= 100,000/mcL - Hemoglobin >= 9 g/dL or >= 5.6 mmol/L - Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 x upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN - Creatinine clearance should be calculated per institutional standard - Serum total bilirubin =< 1.5 x ULN - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR < 5 x ULN for subjects with liver metastases - International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants - Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required - Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year - Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Exclusion Criteria: - Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment - Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier; denosumab is allowed as long as not < 1 week prior to study day 1 and not administered on day of MK-3475 infusion - Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent - Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study - Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy - Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment - Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study - Has evidence of interstitial lung disease or active, non-infectious pneumonitis that required oral or intravenous glucocorticoids to assist with management; lymphangitic spread of the non-small cell lung cancer (NSCLC) is not exclusionary - Has an active infection requiring intravenous systemic therapy - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator - Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial - History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator; myocardial infarction within 6 months prior to enrollment - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment - Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) - Known hypersensitivity to afatinib or the excipients of any of the trial drugs - Prior participation in an afatinib clinical study, even if not assigned to afatinib treatment - Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) - Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) - Has received a live vaccine within 30 days prior to the first dose of trial treatment - The presence of poorly controlled gastrointestinal disorders that could affect the absorption of the afatinib (e.g. --- L858R --- --- L861Q ---

This phase III trial compares the effect of bevacizumab and AZD9291 (osimertinib) combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.

NCT04181060

Conditions

1. Advanced Lung Non-Squamous Non-Small Cell Carcinoma
2. Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
3. Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
4. Stage IIIB Lung Cancer AJCC v8
5. Stage IV Lung Cancer AJCC v8
6. Stage IVA Lung Cancer AJCC v8
7. Stage IVB Lung Cancer AJCC v8

Interventions

1. Biological: Bevacizumab
2. Drug: Osimertinib

MeSH:Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Carcinoma Neoplasm of the lung Non-small cell lung carcinoma

All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 8th edition staging criteria - Patient must have somatic activating sensitizing mutation in EGFR (e.g. but not limited to Exon 19 deletion, L858R, G709X, G719X, exon 19 insertions, L861Q, S768I). --- L858R --- --- L861Q ---

A phase IIb, open-label, single-arm study to assess the safety and efficacy of BPI-7711 capsule in patients with metastatic or recurrent non-small cell lung cancer with EGFR mutation and T790M mutation positive.

NCT03812809

Conditions

1. NSCLC

Interventions

1. Drug: BPI-7711

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). --- L858R --- --- L861Q ---

This study is a multi-center, open-label, dose-finding phase Ib clinical study with extension phase, which is aimed at evaluating the efficacy and safety of GB226 combined with fruquintinib in treatment of relapsed or metastatic NSCLC patients with EGFR-sensitive mutations who have failed to respond to EGFR-TKI treatment,evaluating the pharmacokinetic characteristics of GB226 and fruquintinib, and the immunogenicity of GB226, and preliminarily evaluating the antitumor activity of GB226 and fruquintinib.

NCT03976856

Conditions

1. Metastatic Non-small Cell Lung Cancer

Interventions

1. Drug: GB226
2. Drug: Fruquintinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

To evaluate the immunogenicity of GB226 in Chinese patients with lung cancer.. Inclusion Criteria: 1. Aged 18-75 years, male or female; 2. Understanding the procedures and contents of the study, and voluntarily signing the written informed consent form; 3. Histologically or cytology confirmed relapsed or metastatic NSCLC; 4. EGFR gene sensitive mutation is confirmed positive, any of following is met: exon 19 deletion (19DEL), exon 21 point mutation (L858R / L861Q), 18 exon point mutation (G719X), 20 exon point mutation (S768I). --- L858R --- --- L861Q ---

Inclusion Criteria: 1. Aged 18-75 years, male or female; 2. Understanding the procedures and contents of the study, and voluntarily signing the written informed consent form; 3. Histologically or cytology confirmed relapsed or metastatic NSCLC; 4. EGFR gene sensitive mutation is confirmed positive, any of following is met: exon 19 deletion (19DEL), exon 21 point mutation (L858R / L861Q), 18 exon point mutation (G719X), 20 exon point mutation (S768I). --- L858R --- --- L861Q ---

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Patients with Locally Advanced/Metastatic Non Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours are Epidermal Growth Factor Receptor Mutation and T790M Mutation Positive

NCT02094261

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: AZD9291

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). --- L858R --- --- L861Q ---

This study will treat patients with advanced NSCLC who have already received at least one course of specific anti-cancer treatment but the tumour has started to re-grow following that treatment. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment, it will measure the levels of drug in the body, it will also measure the anti-cancer activity. By using these pieces of information together the best dose of this drug to use in further clinical trials will be selected.

NCT01802632

Conditions

1. Advanced Non Small Cell Lung Cancer
2. Advanced (Inoperable) Non Small Cell Lung Cancer

Interventions

1. Drug: AZD9291

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- Patients (with the exception of 1st line expansion cohort) must fulfil one of the following: - Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR - Must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria (Jackman et al 2010) followed by systemic objective progression (RECIST or WHO) while on continuous treatment with EGFR TKI. - Previous treatment with a single-agent EGFR TKI (e.g. --- L858R --- --- L861Q ---

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of SH-1028 with Locally Advanced/Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene.

NCT03823807

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: SH-1028

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR-TKI sensitivity (including exon 19 deletion, L858R, L861Q, G719X or dual mutation) for treatment-naive NSCLC patients (without systemic therapy or with relapse after previous surgery; patients with locally treatment for non-target lesions are accepted ).(This criteria applies to treatment-naïve NSCLC patients in Part B). - Patients must have confirmation of T790M+ mutation status, which have experienced disease progression while on a previous continuous treatment with an EGFR-TKI or clinical benefit from EGFR-TKI according to the Jackman criteria while on continuous treatment with an EGFR-TKI (PR/CR, or SD continued ≥6 months); Patients can receive more than one line of systemic therapy. --- L858R --- --- L861Q ---

This study is a randomized, single-center, open-label, phase II clinical trial designed to evaluate non-small cell lung cancer that has failed to undergo excessive platinum-based chemotherapy and has not received excessive statin chemotherapy and has not received immunotherapy. The efficacy and safety of Nivolumab in combination with docetaxel and Nivolumab in patients. Qualified patients were stratified by histological type (squamous cell carcinoma vs. non-squamous cell carcinoma) randomized to receive the following regimen in a 1:1 ratio: Group A: Nivolumab 300mg + docetaxel 75mg/m2 IV q3w Group B: Nivolumab 200mg IV q2w All patients were evaluated for tumor at baseline, and tumor evaluations were performed every 6 weeks within 48 weeks after randomization (regardless of whether dosing was delayed). After the 48th week of assessment, a tumor assessment is required every 9 weeks until disease progression, withdrawal of informed consent, sponsor termination study, or patient death.

NCT04023617

Conditions

1. Carcinoma, Non-Small-Cell Lung
2. Docetaxel
3. Nivolumab

Interventions

1. Drug: Nivolumab

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

3. The patient's tumor must be free of EGFR gene-sensitive mutations (including but not limited to exon 19 deletion mutation or exon 21 L858R mutation, exon 21 L861Q, exon 18 G719X or exon 20 S768I site Mutation) and ALK gene rearrangement. --- L858R --- --- L861Q ---

This is an open-label phase 1, safety, PK, and preliminary efficacy study of oral Gefitinib and IV Tremelimumab in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as Erlotinib or Gefitinib. The primary objective of this phase I, is to determine the safety and tolerability of oral Gefitinib in combination with escalating doses of Tremelimumab and to establish a recommended phase 2 dose. Secondary objectives include evaluation of, pharmacokinetics, immunogenicity, antitumor activity of Gefitinib and Tremelimumab combination. The exploratory objectives are to evaluate biomarkers that may correlate with activity or prospectively identify patients likely to respond to Tremelimumab and Gefitinib. The biological rationale for such a study is that even though the disease is progressing it is likely that EGFR sensitive clones, although diminished under the pressure from the EGFR TKI, are still present. Therefore, withdrawing the inhibitory pressure of the EGFR TKI can potentially allow regrowth of the EGFR sensitive cells. On the other hand, the proliferation of EGFR resistant clones needs to be suppressed by another therapeutic approach. Until today no association of chemotherapy and TKI EGFR has demonstrated clinical benefit. Moreover, patients may have received chemotherapy and the likelihood of chemosensitivity is very low. So, the association of Gefitinib with immune checkpoint blockade is very attractive and may result in clinical benefit in NSCLC with EGFRmut.

NCT02040064

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: Gefitinib
2. Drug: Tremelimumab

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Inclusion Criteria: 1. Provision of written informed consent ; 2. Female or male patients aged 18 years or over at the time of consent ; 3. World Health Organisation (WHO) Performance Status 0 to 1 (Appendix C) ; 4. Cytologically or histologically confirmed NSCLC with an activating EGFR TK mutations known to be associated with EGFR TKI sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) as determined locally using a well-validated and robust methodology ; 5. Prior objective clinical benefit defined by either partial, complete or SD (>/= 4months) after initiation of EGFR TKI treatment ; 6. Patients could have received first line chemotherapy or chemotherapy between the EGFR TKI and inclusion in the study but must present a systemic objective progression ; 7. A washout period is not required for patients who are being treated with Gefitinib at the time of study entry. --- L858R --- --- L861Q ---

- Previous allogenic bone marrow transplant Inclusion Criteria: 1. Provision of written informed consent ; 2. Female or male patients aged 18 years or over at the time of consent ; 3. World Health Organisation (WHO) Performance Status 0 to 1 (Appendix C) ; 4. Cytologically or histologically confirmed NSCLC with an activating EGFR TK mutations known to be associated with EGFR TKI sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) as determined locally using a well-validated and robust methodology ; 5. Prior objective clinical benefit defined by either partial, complete or SD (>/= 4months) after initiation of EGFR TKI treatment ; 6. Patients could have received first line chemotherapy or chemotherapy between the EGFR TKI and inclusion in the study but must present a systemic objective progression ; 7. A washout period is not required for patients who are being treated with Gefitinib at the time of study entry. --- L858R --- --- L861Q ---

The purpose of this study is to assess the safety and tolerability of ASP8273 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). This study will also determine the pharmacokinetics (PK) of ASP8273, evaluate the potential inhibition of CYP3A4 by ASP8273 and the antitumor activity of ASP8273 as well as determine the effect of food on the bioavailability of ASP8273.

NCT02113813

Conditions

1. Non-Small-Cell Lung Cancer (NSCLC)
2. Epidermal Growth Factor Receptor Mutations

Interventions

1. Drug: naquotinib
2. Drug: midazolam

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed according to RECIST 1.1, whichever occurs first.. Inclusion Criteria: - Non-child bearing potential or able to follow birth control requirements - Eastern Cooperative Oncology Group (ECOG) ≤ 1 - Life expectancy ≥ 12 weeks - Laboratory criteria as: - Neutrophil count ≥ 1,500/mm3 - Platelet count ≥ 7.5 x 104 /mm3 - Hemoglobin ≥ 9.0 g/dL - Lymphocyte count ≥ 500/mm3 - Serum creatinine < 1.5 x institutional Upper Limit of Normal (ULN) or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation - Total bilirubin < 1.5 x ULN (except for subjects with documented Gilbert's syndrome) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x ULN - Dose escalation subjects: Epidermal Growth Factor Receptor (EGFR) activating mutation by local testing: exon 18 G719X, exon 19 deletion, exon 21 L861Q, exon 21 L858R or exon 20 insertion; and received prior treatment with EGFR Tyrosine Kinase Inhibitor (TKI) - Response expansion/RP2D expansion/ FE Cohort subjects: disease progression on or was intolerant to prior EGFR TKI; activating mutation as above AND T790M mutation; tumor sample subsequent to EGFR TKI is available for central testing; at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Inclusion Criteria for Exon 20 cohort: - Subject on any line of treatment and has an EGFR exon 20 insertion mutation on examination of an NSCLC tissue or cellular specimen. --- L861Q ---

Exclusion Criteria: - Any ongoing toxicity ≥ Grade 2 attributable to prior Non-Small-Cell Lung Cancer (NSCLC) treatment - Prior EGFR inhibitor within 6 days; received prior treatment with any other agent with antitumor activity chemotherapy, radiotherapy, or immunotherapy within 14 days; any investigational therapy within 28 days or 5 half-lives, whichever is shorter; blood transfusion or hemopoietic factor within 14 days; major surgery within 14 days; any strong CYP3A4 inhibitors within 7 days - Positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) or Human Immunodeficiency Virus (HIV) - Symptomatic Central Nervous System (CNS) metastasis - Active infection requiring systemic therapy within 14 days - Severe or uncontrolled systemic diseases including uncontrolled hypertension - History of or active interstitial lung disease - Screening QTcF >450 msec or current medication known to prolong QT - ≥ Grade 2 cardiac arrhythmia or uncontrolled atrial fib of any grade; Class 3 or 4 New York Heart Association congestive heart failure; history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months - History of gastrointestinal ulcer or bleeding within 3 months; any digestive tract dysfunction - Concurrent corneal disorder or ophthalmologic condition making subject unsuitable - RP2D cohort subjects: contraindications to midazolam, any other midazolam within 7 days, or any medications or supplements known to be strong CYP3A inhibitors within 7 days or inducers within 12 days - Any other malignancy requiring treatment Inclusion Criteria: - Non-child bearing potential or able to follow birth control requirements - Eastern Cooperative Oncology Group (ECOG) ≤ 1 - Life expectancy ≥ 12 weeks - Laboratory criteria as: - Neutrophil count ≥ 1,500/mm3 - Platelet count ≥ 7.5 x 104 /mm3 - Hemoglobin ≥ 9.0 g/dL - Lymphocyte count ≥ 500/mm3 - Serum creatinine < 1.5 x institutional Upper Limit of Normal (ULN) or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation - Total bilirubin < 1.5 x ULN (except for subjects with documented Gilbert's syndrome) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x ULN - Dose escalation subjects: Epidermal Growth Factor Receptor (EGFR) activating mutation by local testing: exon 18 G719X, exon 19 deletion, exon 21 L861Q, exon 21 L858R or exon 20 insertion; and received prior treatment with EGFR Tyrosine Kinase Inhibitor (TKI) - Response expansion/RP2D expansion/ FE Cohort subjects: disease progression on or was intolerant to prior EGFR TKI; activating mutation as above AND T790M mutation; tumor sample subsequent to EGFR TKI is available for central testing; at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Inclusion Criteria for Exon 20 cohort: - Subject on any line of treatment and has an EGFR exon 20 insertion mutation on examination of an NSCLC tissue or cellular specimen. --- L861Q ---

This is a Phase 2, open-label, multicenter study to evaluate the efficacy and the safety/tolerability of poziotinib in five patient cohorts for up to 150 previously treated patients with any systemic therapy (Cohort 1: 30 Patients that have HER2-positive or HER2-negative breast cancer with HER2 activating mutations, Cohort 2: 30 Patients that have colorectal cancer with HER2 activating mutations, Cohort 3: Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations, Cohort 4: 30 Patients that have high-grade glioma with EGFR activating mutations, and Cohort 5: 30 Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations.

NCT04172597

Conditions

1. Breast Cancer
2. Colorectal Cancer
3. Solid Tumor
4. High Grade Glioma

Interventions

1. Drug: Poziotinib Hydrochloride

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

EGFR Activating Mutations (at least one of the following) Extracellular & Transmembrane: EGFRvIII, R108K, R222C, A289T, P596L, G598V Kinase Domain: Exon 20 insertion, E709K, G719X, V742I, E746_A750del, S768I, V769M, V774M, R831C, R831H, L858R, L861Q, A864V 5. Patient has measurable disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and/or RANO Criteria for Cohort 4. These target lesion(s) must be radiographically measurable. --- R108K --- --- R222C --- --- A289T --- --- P596L --- --- G598V --- --- E709K --- --- V742I --- --- S768I --- --- V769M --- --- V774M --- --- R831C --- --- R831H --- --- L858R --- --- L861Q ---

This study has two parts: dose escalation and dose expansion. The primary objectives are: - For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with gefitinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with gefitinib in the study population - For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with gefitinib in the study population. In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles. The number of treatment cycles is not fixed in this study. Participants will continue study treatment for 36 months unless they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity).

NCT03599518

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: DS-1205c
2. Drug: Gefitinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Inclusion Criteria: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 3. Has acquired resistance to EGFR tyrosine kinase inhibitor (TKI) according to the Jackman criteria (PMID: 19949011): 1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression [Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 4. Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib 5. Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day 6. Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, afatinib, or osimertinib 7. Has at least one measurable lesion per RECIST version 1.1 8. --- L858R --- --- L861Q ---

Has history of pancreatitis within the past 6 months Inclusion Criteria: 1. Has histologically or cytologically documented adenocarcinoma NSCLC 2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation 3. Has acquired resistance to EGFR tyrosine kinase inhibitor (TKI) according to the Jackman criteria (PMID: 19949011): 1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR 2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression [Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI 4. Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib 5. Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day 6. Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, afatinib, or osimertinib 7. Has at least one measurable lesion per RECIST version 1.1 8. --- L858R --- --- L861Q ---

The purpose of this open-label, single-arm, multi-center phase II trial is to evaluate the efficacy and safety of novel pan-HER inhibitor, NOV120101 (Poziotinib), as a 2nd line monotherapy agent in lung adenocarcinoma patients with acquired resistance to prior EGFR tyrosine kinase inhibitors (TKIs).

NCT01718847

Conditions

1. Increased Drug Resistance

Interventions

1. Drug: NOV120101 (Poziotinib)

Inclusion Criteria: 1. Male or female patients aged 20 years or older 2. Pathologically confirmed stage IIIB (unresectable) or IV lung adenocarinoma 3. Patients who have 1 or more than 1 measurable or evaluable but unmeasurable lesions according to RECIST ver1.1 4. Patients who received prior 1st generation EGFR TKIs (gefitinib or erlotinib) monotherapy and meet the following criteria: 1. Patients with EGFR mutation (e.g., G719X, exon 19 deletion, L858R, L861Q, etc) known to be associated with sensitivity to TKIs 2. Patients who showed objective clinical benefit from treatment with an EGFR TKI as defined by either: - Patients who showed complete (CR) or partial response (PR), or - Patients who maintained stable disease (SD) status ≥ 6 months 3. Patients who showed progressive disease (PD, RECIST ver1.1) while on continuous treatment with gefitinib or erlotinib within the last 30 days (However, patients whose progressive disease is limited in the brain cannot participate in this trial.) --- L858R --- --- L861Q ---

Patients who cannot participate in this trial by investigator's judgment Inclusion Criteria: 1. Male or female patients aged 20 years or older 2. Pathologically confirmed stage IIIB (unresectable) or IV lung adenocarinoma 3. Patients who have 1 or more than 1 measurable or evaluable but unmeasurable lesions according to RECIST ver1.1 4. Patients who received prior 1st generation EGFR TKIs (gefitinib or erlotinib) monotherapy and meet the following criteria: 1. Patients with EGFR mutation (e.g., G719X, exon 19 deletion, L858R, L861Q, etc) known to be associated with sensitivity to TKIs 2. Patients who showed objective clinical benefit from treatment with an EGFR TKI as defined by either: - Patients who showed complete (CR) or partial response (PR), or - Patients who maintained stable disease (SD) status ≥ 6 months 3. Patients who showed progressive disease (PD, RECIST ver1.1) while on continuous treatment with gefitinib or erlotinib within the last 30 days (However, patients whose progressive disease is limited in the brain cannot participate in this trial.) --- L858R --- --- L861Q ---

The purpose of this study is to determine whether continuing erlotinib beyond disease progression in combination with chemotherapy is beneficial for NSCLC patients who have EGFR mutant disease or who have responded to EGFR TKI.

NCT02064491

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Erlotinib
2. Drug: Chemotherapy

MeSH:Carcinoma, Non-Small-Cell Lung Disease Progression

HPO:Non-small cell lung carcinoma

- Investigator confirmed progression according RECIST 1.1 during EGFR TKI treatment within 28 days of the randomization - Activating mutation (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) in the EGFR gene or have had at least partial response with EGFR TKI lasting ≥ 6 months - Performance status: WHO 0-2 - Measurable disease according to RECIST 1.1 - Patients must be able to comply with study treatments - Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study - Neutrophils ≥ 1'000/μl, Platelets ≥ 100'000/μl, Alanine amino transferase ≤ 2.5 × Upper limit of normal (ULN) (< 5 × ULN if liver metastases), Alkaline phosphatase ≤ 2.5 × ULN (< 5 × ULN if liver metastases), Serum bilirubin ≤ 1.5 × ULN, Serum Creatinine ≤ 1.5 × ULN. - Patient must be able to comply with the protocol Exclusion Criteria: - RECIST 1.1 defined disease progression for more than 28 days while on previous EGFR TKI treatment. --- G719A --- --- L858R --- --- L861Q ---

using Atezolizumab, a PD-L1 inhibitor, in combination with bevacizumab, platinum and pemetrexed to treat patients with EGFR mutated, advanced non-small cell lung cancer (NSCLC) after failure of EGFR tyrosine kinase inhibitors.

NCT04147351

Conditions

1. NSCLC Stage IIIB~IV

Interventions

1. Drug: Atezolizumab Injection; bevacizumab Injection

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

EGFR activating mutations include exon19 deletion, L858R, G719X, L861Q, or S768I. --- L858R --- --- L861Q ---

This is a multicentre, open-label, uncontrolled, Phase Ib clinical study. Patients who give informed consent will be screened for the study, including genotyping of the tumour and baseline characteristics. Eligible patients will receive a single pre-treatment of low dose of intravenous cyclophosphamide 200 mg/m2 (Day -3). Patients will commence daily oral therapy with the EGFR TKI afatinib as soon as possible, preferably on the same day as low dose cyclophosphamide. Afatinib will be prescribed according to the Summary of Product Characteristics (SmPC) of the product, and will continue in nominal 21-day cycles for as long as clinically indicated. The first day of dosing with EGF-PTI will be designated Day 1. Immunisation with EGF-PTI will commence 3 days after low dose cyclophosphamide and commencement of EGFR TKI, and will be repeated on Day 14, Day 28, Day 43, and Day 92. After the 5 th vaccination, patients will be followed up every 6 weeks for basic safety data and every 3 months for complete efficacy data, safety data, and maintenance (reduced) doses of EGF-PTI. Patients will continue in the study until disease progression, death, safety concerns (in the opinion of the investigator), non-compliance with the protocol, the patient withdraws from the study, 1 year after randomisation of the last patient, or the study is stopped the sponsor, whichever occurs sooner

NCT03623750

Conditions

1. Carcinoma, Non-Small-Cell Lung

Interventions

1. Drug: EGFR-TK Inhibitor
2. Biological: EGF-PTI
3. Drug: Cyclophosphamide

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

4. Centrally confirmed EGFR exon 19 deletion, exon 21 (L858R, L861Q) or exon 18 (G719X) mutation before treatment (concomitant T790M pre-treatment mutation is permitted). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. --- L858R --- --- L861Q ---

Preclinical data in lung cancer cell lines showed that EGFR mutation can potentially be a positive predictor for sensitivity to BKM120. Furthermore, when the erlotinib-resistant model H1975 (LR858 and T790M mutation) was treated with BKM120, significant tumor control was observed (Novartis internal data). Therefore, combining BKM120 with erlotinib could potentially down-modulate PI3K-Akt activity resulting in a synergistic effect on cell growth inhibition and enhancing the response to erlotinib.

NCT01487265

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: BKM120 and Erlotinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

These include, but are not limited to mutations in L858R (Exon 21); Exon 19 deletion; G719S, G719A, G719C mutations (Exon 19);or L861Q (laboratory report required at enrollment). --- L858R --- --- G719S --- --- G719A --- --- G719C --- --- L861Q ---

This is an open-label, non-randomized, multicenter phase Ib/II study, which is composed of a phase Ib dose escalation part and a phase II dose expansion part. Patients will receive selumetinib in combination with gefitinib 250mg daily. This study will enroll EGFR-mutated NSCLC patients who have developed acquired resistance to EGFR TKI treatment.

NCT02025114

Conditions

1. Non-small Cell Lung Cancer (NSCLC)

Interventions

1. Drug: selumetinib

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

A tumor harboring an EGFR mutation known to be associated with drug sensitivity (ie, exon 19 deletion , L858R, L861Q, G719X etc.). --- L858R --- --- L861Q ---

This is a 2-part study in patients with epidermal growth factor receptor mutation positive (EGFRm+) non-small cell lung cancer (NSCLC) whose disease has progressed on treatment with an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI): Part A will determine the effect of food on the pharmacokinetics (PK) of AZD9291; Part B will allow patients further access to AZD9291 and will provide for additional safety data collection. Part A is a randomised, open-label, 2 treatment period crossover study in which patients will each receive a single oral dose of AZD9291 (1 x 80 mg tablet) at breakfast time (approximately 0800) in each of 2 treatment periods (once immediately following a high fat meal [fed], and once in the fasted state [fasted]), with a washout period of 9 days between doses. Approximately 38 patients are planned to be enrolled and dosed; at least 30 evaluable patients will be required to complete Part A (ie, the last PK sample in Treatment Period 2 [TP 2] has been collected). Additional patients may be enrolled to allow for at least 30 evaluable patients.

NCT02163733

Conditions

1. Advanced Non Small Cell Lung Cancer
2. Advanced (Inoperable) Non Small Cell Lung Cancer

Interventions

1. Drug: AZD9291 tablets
2. Procedure: Pharmacokinetic sampling - AZD9291
3. Other: Dietary Fasted
4. Other: Dietary High Fat
5. Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

5. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). --- L858R --- --- L861Q ---

The current first line treatment of patients with EGFR activating mutation lung cancer is EGFR TKI. Compared to platinum-based chemotherapy, EGFR-TKIs are superior in terms of response rate and progression-free survival. However, an acquired resistance occurs almost constantly. The second-line treatment includes platinum-based chemotherapy in the absence of contraindication. This chemotherapy is then administered after discontinuing EGFR TKIs. However, a rebound phenomenon of the disease was described in patients who discontinued EGFR TKIs. Some clinical teams therefore recommend, as a precaution, in order to avoid any withdrawal phenomenon, to never discontinue EGFR TKIs in patients developing an EGFR TKI acquired resistance. It seems therefore useful to conduct a study to better define the therapeutic strategy to adopt in patients developing an acquired resistance after having received EGFR TKIs as first line treatment.

NCT02178397

Conditions

1. NSCLC Patients With EGFR Activating Mutation

Interventions

1. Drug: ERLOTINIB WITH CHEMOTHERAPY
2. Drug: CHEMOTHERAPY ONLY

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- Presence of one of the EGFR activating mutations in the tumor (exon 19 deletion or L858R, G719X or L861Q) - One additional line of previous chemotherapy is allowed if administered in adjuvant or neoadjuvant setting and received more than six months before. --- L858R --- --- L861Q ---

To compare clinical response (complete response and partial response) by RECIST) rates by RECIST between erlotinib monotherapy and docetaxel plus cisplatin chemotherapy

NCT02036359

Conditions

1. Non-small Cell Lung Cancer(NSCLC)

Interventions

1. Drug: erlotinib
2. Drug: docetaxel

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

- Life expectancy > 12 weeks - Tumor specimen with EGFR gene mutation of exon 19 deletion and L858R, G719X, L861Q mutation - Adequate hematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL - Data of INR and PTT should be available in patients taking anticoagulants concomitantly, with INR ≤ 1.5 and PTT ≤ 1.5 times the upper limit of normal (x ULN ) within 7 days prior to starting study treatment - Adequate liver function: serum bilirubin ≤ 1.5 x ULN; transaminases ≤ 2.5 x ULN - Adequate renal function: 24-hour urine creatinine clearance or creatinine clearance measured and calculated according to the formula of Cockroft and Gault ≥ 60ml/min - Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women - Written informed consent. --- L858R --- --- L861Q ---

Those with exon 19 deletion and L858R, G719X, L861Q mutation were randomized as erlotinib monotherapy or docetaxel plus cisplatin chemotherapy. --- L858R --- --- L861Q ---

The primary objective is to assess the safety and tolerability of multiple doses of Simotinib Hydrochloride in NSCLC patients. The secondary objective is to determine the pharmacokinetic (PK) profile and explore the preliminary anti-tumor activity.

NCT01772732

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Simotinib Hydrochloride

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Inclusion Criteria: - Patients with histologically or cytologically confirmed diagnosis of advanced NSCLC, who were previously treated with at least one platinum-based chemotherapy regimen, but had disease relapse; - Patients have ended their chemotherapy or radiotherapy at least 4 weeks prior to study entry and have recovered from any previous toxicity; - EGFR mutation positive (such as E19del, L858R, L861Q, G719X, etc.); - Patients with at least one measurable lesion meeting RECIST; - ECOG performance status 0-2; - Life expectancy ≥12 weeks; - Adequate bone marrow function: ANC ≥1.5 × 109/L, PLT≥80 ×109/L, HB ≥90 g/L; - Adequate hepatic function: serum bilirubin ≤ 2 × ULN, AST and ALT ≤ 2.5 × ULN, and ≤ 5 × ULN are acceptable if the liver has tumor involvement; - Adequate renal function: endogenous creatinine clearance rate (CrCl) ≥ 60 mL/min or serum creatinine ≤ 1.5 × ULN; - Females with childbearing potential must have a negative pregnancy test within 7 days prior to treatment and use an approved contraceptive method during the study; - Males must be surgically sterile or use an approved contraceptive method during the study. --- L858R --- --- L861Q ---

This is a 2 part study in patients with EGFRm+ non small cell lung cancer (NSCLC), whose disease has progressed on an EGFRm TKI, who are refractory or resistant to standard therapy. Part A will assess the effect of multiple oral doses of itraconazole on the single dose pharmacokinetic (PK) parameters of AZD9291. On completion of Part A, patients may continue to take AZD9291 tablets (Part B) following the collection of the 216 hour sample on Day 19 if they and the Investigator deem it appropriate, until such time as their disease progresses, the Investigator believes they are no longer deriving clinical benefit, or they stop taking AZD9291 for any other reason.

NCT02157883

Conditions

1. Advanced Non Small Cell Lung Cancer
2. Advanced (Inoperable) Non Small Cell Lung Cancer

Interventions

1. Procedure: Pharmacokinetic sampling
2. Drug: AZD9291
3. Drug: Itraconazole

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. ECOG performance status 0-1 with no deterioration over the previous 2 weeks. --- L858R --- --- L861Q ---

The primary purpose of this study is to compare the efficacy of the study drug LY2875358, given together with erlotinib, against erlotinib, alone. Participants will have Non-Small Cell Lung Cancer (NSCLC) that has advanced to Stage IV. Participants should not have been treated with drugs for Stage IV NSCLC, previously. All participants will get erlotinib alone, for approximately 8 weeks. Participants with radiographic disease control at the end of the erlotinib lead-in study period will be randomly assigned to receive LY2875358 plus erlotinib or erlotinib alone. Participants, who were chosen to receive erlotinib, alone, may cross over to the combination treatment at the time of progression.

NCT01897480

Conditions

1. Carcinoma, Non-Small-Cell Lung

Interventions

1. Biological: LY2875358
2. Drug: Erlotinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of metastatic Stage IV NSCLC - Have at least 1 measurable lesion whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) - Have molecular evidence of an epidermal growth factor receptor mutation (EGFRmt) known to be associated with EGFR tyrosine kinase inhibitor (TKI) drug sensitivity (G719X, exon 19 deletion, L858R, L861Q) - Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 - Haven't received any prior systemic chemotherapy for Stage IV NSCLC (unless received as neoadjuvant or adjuvant therapy for early-stage NSCLC disease and completed therapy at least 6 months prior to enrollment) - Availability of adequate tumor material (block or slides) Exclusion Criteria: - Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device - Have previously completed or withdrawn from this study or any other study investigating LY2875358 - Have a serious concomitant systemic disorder or significant cardiac disease - Have interstitial pneumonia or interstitial fibrosis of the lung or have pleural effusion, pericardial fluids or ascites, requiring drainage every other week or more frequently - Have a history of another malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study - Have major surgery less than 2 weeks prior to the initiation of study treatment therapy - Pregnant or lactating women Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of metastatic Stage IV NSCLC - Have at least 1 measurable lesion whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) - Have molecular evidence of an epidermal growth factor receptor mutation (EGFRmt) known to be associated with EGFR tyrosine kinase inhibitor (TKI) drug sensitivity (G719X, exon 19 deletion, L858R, L861Q) - Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 - Haven't received any prior systemic chemotherapy for Stage IV NSCLC (unless received as neoadjuvant or adjuvant therapy for early-stage NSCLC disease and completed therapy at least 6 months prior to enrollment) - Availability of adequate tumor material (block or slides) Exclusion Criteria: - Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device - Have previously completed or withdrawn from this study or any other study investigating LY2875358 - Have a serious concomitant systemic disorder or significant cardiac disease - Have interstitial pneumonia or interstitial fibrosis of the lung or have pleural effusion, pericardial fluids or ascites, requiring drainage every other week or more frequently - Have a history of another malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study - Have major surgery less than 2 weeks prior to the initiation of study treatment therapy - Pregnant or lactating women Carcinoma, Non-Small-Cell Lung Carcinoma, Non-Small-Cell Lung null --- L858R --- --- L861Q ---

Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of metastatic Stage IV NSCLC - Have at least 1 measurable lesion whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) - Have molecular evidence of an epidermal growth factor receptor mutation (EGFRmt) known to be associated with EGFR tyrosine kinase inhibitor (TKI) drug sensitivity (G719X, exon 19 deletion, L858R, L861Q) - Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 - Haven't received any prior systemic chemotherapy for Stage IV NSCLC (unless received as neoadjuvant or adjuvant therapy for early-stage NSCLC disease and completed therapy at least 6 months prior to enrollment) - Availability of adequate tumor material (block or slides) Exclusion Criteria: - Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device - Have previously completed or withdrawn from this study or any other study investigating LY2875358 - Have a serious concomitant systemic disorder or significant cardiac disease - Have interstitial pneumonia or interstitial fibrosis of the lung or have pleural effusion, pericardial fluids or ascites, requiring drainage every other week or more frequently - Have a history of another malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study - Have major surgery less than 2 weeks prior to the initiation of study treatment therapy - Pregnant or lactating women Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of metastatic Stage IV NSCLC - Have at least 1 measurable lesion whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) - Have molecular evidence of an epidermal growth factor receptor mutation (EGFRmt) known to be associated with EGFR tyrosine kinase inhibitor (TKI) drug sensitivity (G719X, exon 19 deletion, L858R, L861Q) - Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 - Haven't received any prior systemic chemotherapy for Stage IV NSCLC (unless received as neoadjuvant or adjuvant therapy for early-stage NSCLC disease and completed therapy at least 6 months prior to enrollment) - Availability of adequate tumor material (block or slides) Exclusion Criteria: - Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device - Have previously completed or withdrawn from this study or any other study investigating LY2875358 - Have a serious concomitant systemic disorder or significant cardiac disease - Have interstitial pneumonia or interstitial fibrosis of the lung or have pleural effusion, pericardial fluids or ascites, requiring drainage every other week or more frequently - Have a history of another malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study - Have major surgery less than 2 weeks prior to the initiation of study treatment therapy - Pregnant or lactating women Carcinoma, Non-Small-Cell Lung Carcinoma, Non-Small-Cell Lung null --- L858R --- --- L861Q --- --- L858R --- --- L861Q ---

The purpose of this study is to compare the efficacy of TAK-788 as first-line treatment with that of platinum-based chemotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

NCT04129502

Conditions

1. Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)

Interventions

1. Drug: TAK-788
2. Drug: Pemetrexed
3. Drug: Cisplatin
4. Drug: Carboplatin

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Higher scores represent a high level of symptomatology/problems.. Inclusion Criteria: - Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) non-small cell lung cancer (NSCLC) - Documented epithelial growth factor receptor (EGFR) in-frame exon 20 insertion mutation assessed by a clinical laboratory improvements amendment (CLIA)-certified (United States [US] sites) or an accredited (outside of the US) local laboratory The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations except EGFR mutations for which there are approved anti-EGFR TKIs (ie, exon 19 del, L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid) - Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR exon 20 insertion mutation - At least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version 1.1 - Life expectancy ≥3 months - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Exclusion Criteria: - Received prior systemic treatment for locally advanced or metastatic disease - Received radiotherapy ≤14 days before randomization or has not recovered from radiotherapy-related toxicities - Received a moderate or strong cytochrome P-450 (CYP)3A inhibitor or moderate or strong CYP3A inducer within 10 days before randomization - Have been diagnosed with another primary malignancy other than NSCLC - Have current spinal cord compression or leptomeningeal disease - Have uncontrolled hypertension. --- L858R --- --- T790M --- --- L861Q ---

Participants with hypertension should be under treatment on study entry to control blood pressure - Received a live vaccine within 4 weeks before randomization per Summary of product characteristics (SmPCs) for pemetrexed, cisplatin, and carboplatin Inclusion Criteria: - Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) non-small cell lung cancer (NSCLC) - Documented epithelial growth factor receptor (EGFR) in-frame exon 20 insertion mutation assessed by a clinical laboratory improvements amendment (CLIA)-certified (United States [US] sites) or an accredited (outside of the US) local laboratory The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations except EGFR mutations for which there are approved anti-EGFR TKIs (ie, exon 19 del, L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid) - Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR exon 20 insertion mutation - At least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version 1.1 - Life expectancy ≥3 months - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Exclusion Criteria: - Received prior systemic treatment for locally advanced or metastatic disease - Received radiotherapy ≤14 days before randomization or has not recovered from radiotherapy-related toxicities - Received a moderate or strong cytochrome P-450 (CYP)3A inhibitor or moderate or strong CYP3A inducer within 10 days before randomization - Have been diagnosed with another primary malignancy other than NSCLC - Have current spinal cord compression or leptomeningeal disease - Have uncontrolled hypertension. --- L858R --- --- T790M --- --- L861Q ---

This is a Phase 1, open-label study of SH-1028 with dose escalation and dose expansion cohorts in locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients who have progressed following prior therapy with an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor (TKI) agent.

NCT03603262

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: SH-1028

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

5. Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria while on continuous treatment with an EGFR TKI(PR/CR, or SD continued ≥6 months). --- L858R --- --- L861Q ---

This is a phase II trial of durvalumab in combination of platinum-based chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human immunodeficiency virus (HIV) infection (cohort 1) or hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (cohort 2) will be eligible. Patients will receive standard platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. We hypothesized that Durvalumab in combination with standard chemotherapy is safe and effective for the treatment of stage IV NSCLC in patients with HIV, HBV, or HCV infection.

NCT04499053

Conditions

1. Carcinoma, Non-Small Cell Lung

Interventions

1. Drug: Durvalumab

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Exclusion Criteria: 1. Sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q) and/or ALK translocations by locally approved laboratory testing including blood-based liquid biopsy. --- L858R --- --- L861Q ---

This is a Phase 1/2, open-label, multicenter study of HS-10296 with dose escalation, dose expansion and extension cohorts in locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients who have progressed following prior therapy with an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor (TKI) agent. The study is designed to evaluate safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of once-daily and orally (PO) administered HS-10296. The overall study design is shown in the flow chart below, which consists of 3 phases: dose escalation, dose expansion and extension cohort.

NCT02981108

Conditions

1. Nonsmall Cell Lung Cancer

Interventions

1. Drug: HS-10296

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

5. Patients must fulfill one of the following: - Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria (followed by systemic objective progression (RECIST or World Health Organization [WHO]) while on continuous treatment with an EGFR TKI. 6. --- L858R --- --- L861Q ---

third generation of EGFR-TKIs is the newest target therapy for NSCLC. However, we did not known the specific mechanisms for those non-responders and patients grow resistance.Next generation sequencing is current the most sensitive and specific method to exam gene mutation, diversion etc. By consistently detect the cf-DNA, we could possibly find out the mechanisms of response and resistance.

NCT02738593

Conditions

1. Non-small Cell Lung Cancer

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

- harboured with positive EGFR mutation (19 exon deletion, L858R, G719X, L861Q mutation) - reliable patients history data. --- L858R --- --- L861Q ---