To assess the efficacy and safety of Almonertinib versus placebo in patients with epidermal growth factor receptor mutation-positive (EGFRm+) stage II-IIIB non-small cell lung cancer (NSCLC), following complete tumor resection with or without adjuvant chemotherapy.

NCT04687241

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Almonertinib
2. Drug: Placebo Almonertinib

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

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

7. Confirmation by the central laboratory that the tumor harbors 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 including T790M. --- L858R ---

This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutation (exon 19 deletion or exon 21 L858R point mutation), accompanied with Bim deletion or low activating EGFR mutation abundance.

NCT03267654

Conditions

1. Non-small-cell Lung Cancer

Interventions

1. Drug: gefitinib combined with chemotherapy
2. Drug: gefitinib combined with apatinib
3. Drug: gefitinib single agent

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Gefitinib With Chemotherapy or Anti-angiogenesis in NSCLC Patients With Bim Deletion or Low EGFR Mutation Abundance This is an open-label, multicenter, randomized, phase II clinical trial, which aims to evaluate the effectiveness and safety of gefitinib versus combination of gefitinib and doublet chemotherapy or apatinib in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutation (exon 19 deletion or exon 21 L858R point mutation), accompanied with Bim deletion or low activating EGFR mutation abundance. --- L858R ---

3. EGFR mutation (exon 19 deletion or exon 21 L858R) with Bim deletion or low abundance for EGFR mutation. --- L858R ---

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 ---

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

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 ---

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 ---

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 ---

1. Gefitinib CTTQ production gefitinib and erlotinib sheet AstraZeneca imatinib sheet (trade name: Iressa ®) comparison, human pharmacokinetics and relative bioavailability of comparative studies which examine people in vivo pharmacokinetic behavior, provide the basis for clinical use. 2. Evaluation CTTQ gefitinib imatinib sheet production efficacy and safety of Chinese patients with locally advanced or metastatic non-small cell lung cancer.

NCT03264794

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Gefitinib Tab （CTTQ），First medication；Gefitinib Tab （CTTQ），From the 8th day of trial
2. Drug: Gefitinib tablets (Yi Ruisha），First medication
3. Drug: Gefitinib Tab 250 MG（CTTQ），From the 8th day of trial.

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

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

Inclusion Criteria: 1. Patients volunteered to participate in this study, signed informed consent; 2. ≥18 years old; ECOG PS score: 0 ~ 1; expected survival period of more than 3 months; 3. patients with locally advanced or metastatic non-small cell lung cancer diagnosed by histology or cytology, who can not receive radical surgery or radiotherapy; patients with measurable lesions(according to RECIST criteria); 4. Detection of EGFR-positive exon 19 deletion or exon 21 (L858R) mutation was performed by providing a detectable specimen (tissue or cancerous pleural effusion) prior to enrollment; 5. --- L858R ---

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 ---

This is a nationwide, multicenter and prospective cohort study. The purpose of this study is to evaluate the synergistic effect and safety of Elemene plus TKIs in EGFR-mutated advanced non-small cell lung cancer.

NCT04401059

Conditions

1. Carcinoma
2. Non-Small-Cell Lung Cancer
3. Adenocarcinoma

Interventions

1. Drug: Elemene plus First-generation EGFR-TKIs
2. Drug: First-generation EGFR-TKIs

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

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

3. Patients with EGFR mutations (deletions in exon 19 and L858R in exon 21 of the EGFR gene), plan to receive First-generation EGFR-TKIs (Gefitinib, Erlotinib, Icotinib) monotherapy for the first time. --- L858R ---

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 ---

- 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 ---

Multicentre, phase II, open-label, single-arm study evaluating the preliminary efficacy, safety and tolerability of atezolizumab in association with palliative radiotherapy in adult patients diagnosed with advanced (stage IV) NSCLC, irrespective of PD-L1 status, and who have oligoprogressed to both immunotherapy with an anti PD-1 agent (e.g., pembrolizumab or nivolumab) and 1 line of chemotherapy.

NCT04549428

Conditions

1. NSCLC Stage IV

Interventions

1. Drug: Atezolizumab

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Inclusion Criteria: - Signed Informed Consent Form - Histologically or cytologically confirmed diagnosis of metastatic (Stage IV) - NSCLC as per the American Joint Committee on Cancer (AJCC) 8th edition - No sensitizing EGFR mutation (L858R or exon 19 deletions), ALK fusion oncogene or ROS1 rearrangement detected - Progressing to one line of chemotherapy defined as follows: 1. --- L858R ---

In the management of non-small cell lung cancer of the adenocarcinoma type, different therapeutic strategies can be proposed. These strategies are defined according to the results of a biological analysis of blood and/or tissue samples from the lung tumor. Mutations in the tumor DNA are sought. Thus, patients with sensitizing mutations can benefit from a treatment with a 3rd generation tyroine kinase inhibitor (TKI) whose efficacy has been widely demonstrated. Patients without tumor mutations will not benefit. However, resistance to TKIs appears after a certain time, often linked to the appearance of new mutations in the tumor. For this reason, blood biologic analyses are regularly performed to search for the emergence of resistance mutations and to propose a therapeutic alternative as soon as possible. These analyses are performed routinely in the laboratory. In the course of these analyses, the investigators have identified conventional mutations but also new mutations not previously described in the literature. Our objective is to list all the molecular abnormalities revealed during blood biological analyses, to determine their frequency and to study whether certain abnormalities can be linked to resistance to TKI.

NCT04546282

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Other: Description of the molecular alterations detected in blood samples of patients treated by osimertinib

MeSH:Lung Neoplasms

HPO:Neoplasm of the lung

Inclusion Criteria: - advanced non-small cell lung cancer stage IIIB/IV - Documentation of activating EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) at the time of initial diagnosis - Patient may receive up to one line of third EGFR TKI - Plasma sample testing performed to detect EGFR TKI resistance Exclusion Criteria: - Patients have other concurrent cancers - Patients who are not eligible receive TKI Inclusion Criteria: - advanced non-small cell lung cancer stage IIIB/IV - Documentation of activating EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) at the time of initial diagnosis - Patient may receive up to one line of third EGFR TKI - Plasma sample testing performed to detect EGFR TKI resistance Exclusion Criteria: - Patients have other concurrent cancers - Patients who are not eligible receive TKI Non Small Cell Lung Cancer Lung Neoplasms null --- L858R ---

Inclusion Criteria: - advanced non-small cell lung cancer stage IIIB/IV - Documentation of activating EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) at the time of initial diagnosis - Patient may receive up to one line of third EGFR TKI - Plasma sample testing performed to detect EGFR TKI resistance Exclusion Criteria: - Patients have other concurrent cancers - Patients who are not eligible receive TKI Inclusion Criteria: - advanced non-small cell lung cancer stage IIIB/IV - Documentation of activating EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) at the time of initial diagnosis - Patient may receive up to one line of third EGFR TKI - Plasma sample testing performed to detect EGFR TKI resistance Exclusion Criteria: - Patients have other concurrent cancers - Patients who are not eligible receive TKI Non Small Cell Lung Cancer Lung Neoplasms null --- L858R --- --- L858R ---

This trial is testing two novel combinations (temozolomide plus osimertinib OR temozolomide plus lorlatinib) which have not been evaluated in clinical trials. Thus, the exact benefits of these novel combinations are unclear. However, based on the mechanism of action of temozolomide and CNS(Central Nervous System) penetration/activity in other tumor types, it is hypothesized that adding temozolomide to osimertinib or temozolomide to lorlatinib may provide improvement in CNS disease control in patients with CNS progression on either of these latter two TKIs (Tyrosine kinase inhibitors).

NCT04541407

Conditions

1. Non Small Cell Lung Cancer
2. CNS Progression

Interventions

1. Drug: Temozolomide plus Osimertinib
2. Drug: Temozolomide plus Lorlatinib

MeSH:Disease Progression

3. Male or female subject ≥ 18 years old 4. ECOG performance status 0-2 5. Stage IV NSCLC with progression of disease in the CNS on osimertinib 80 mg daily for patients with EGFR activating mutations (EGFR exon 19 deletions or EGFR L858R exon 21 point mutations) -OR- Stage IV NSCLC with progression of disease in the CNS on lorlatinib 100 mg daily for patients with ALK fusions 6. Evaluable CNS disease is required, measurable CNS disease is not required 7. Patients who are on corticosteroids must be on stable or decreasing doses of corticosteroids for at least 14 days. --- L858R ---

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 ---

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) such as erlotinib have proved effective in second or third line therapy for advanced non-small cell lung cancer(NSCLC).It is well tolerated without the side effects usually associated with chemotherapy. The mutations in EGFR exons 19 or 21 have been reported to be associated with efficacy of EGFR TKIs.Based on the encouraging preliminary results from the Spanish lung cancer group' prospective study reported that the efficacy of Tarceva as first line treatment for metastatic NSCLC patients with EGFR mutation would delay disease progression,prolong overall survival and be well tolerated, medium Progression-free survival(PFS) was around 12 months and OS reach 24 months，our study is designed to compare PFS between the patients with mutant EGFR treated by gemcitabine/carboplatin and those by erlotinib in the first-line setting. We assumed 11 months of PFS on Tarceva arm versus 6 months on chemotherapy arm with a=0.025(alpha-spend for an interim analysis), 80% power and 12 months enrolment period, 12 months FU duration to calculate the sample size. The sample size is 69 pairs. Considering about 10% drop-out rate, the final sample size is 152 patients.So, chemo-naive staged IIIb/IV patients with EGFR mutations in exon 19 or 21 will be enrolled into this open-label, randomized,multicenter phase III study.

NCT00874419

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: erlotinib
2. Drug: gemcitabine/carboplatin

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

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

2. EGFR exon19 deletions or exon 21 L858R mutation by the DNA direct PCR sequencing using fresh tumor sample or paraffin embed tumor sample. --- L858R ---

This is an open label, non-randomized, sequential, phase I/II trial in patients with stage IIIB or IV non-small cell lung cancer (NSCLC) with EGFR mutations after progression to Erlotinib. The study will have two parts. The first part (phase I) will be a dose finding (MTD) study to be implemented at three hospitals. The second part of the study (phase II) will asses the safety and efficacy of the combination. In this second part (phase II) patients will be treated with oral Erlotinib 150 mg P.O daily plus oral Vorinostat administered according to the results of the phase I. The study endpoints to be evaluated will include safety and response rate (RR) as primary endpoints and clinical benefit rate (CBR), time to progression, time to response, response duration and progression free survival as secondary endpoints. All the patients (phase I and II) will be treated until progression disease, unacceptable toxicity or withdrawal of the consent, and will be treated at the discretion of the principal investigator.

NCT00503971

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Vorinostat plus Erlotinib

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

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

4. Have demonstrated mutations at epidermal growth factor receptor (EGFR) at Exon 19 or Exon 21 (Exon 19 mutations characterized by in-frame deletions (747-750), and Exon 21 mutations resulting in L858R substitutions). --- L858R ---

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 ---

The main objective of this study is to evaluate the safety and tolerability of BPI-15086.

NCT02914990

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: BPI-15086

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

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

icotinib, gefitinib, afatinib, neratinib, dacomitnib, or erlotinib) treatment - Patients must fulfil one of the following: - Confirmation that the tumour harbours EGFR sensitivity mutation (exon 19 deletion, L858R and L861R, G719X) - Must have experienced clinical benefit from EGFR TKIs, according to the Jackman criteria - Confirmation of T790M mutation positive after disease progression on EGFR TKIs - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and estimated life expectancy of at least 12 weeks - Measurable lesion per Response Evaluation Criteria in Solid Tumors(RECIST1.1) --- L858R ---

The phase II APPLE trial gives the opportunity to prospectively validate liquid biopsies as a new standard for testing tumor progression compared with conventional radiological procedure in EGFR mutant advanced NSCLC patients. Moreover based on the sequential T790M test during treatment the investigators will assess the predictive value of liquid biopsies. APPLE trial will examine the best strategy for delivering osimertinib (upfront versus sequential treatment after 1st generation EGFR TKI) in EGFR mutant NSCLC patients. Finally, the trial will also explore the mechanisms of acquired resistance to Osimertinib based on the results of an optional biopsy upon progression.

NCT02856893

Conditions

1. NSCLC

Interventions

1. Drug: Osimertinib
2. Drug: Gefitinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Adverse events, serious adverse events and adverse reactions will be monitored.. Inclusion: Registration: - Pathological diagnosis of adenocarcinoma of the lung carrying common EGFR activating mutations associated with EGFR-TKI sensitivity (Del19 or L858R); performed locally; no other EGFR mutations will be allowed. --- L858R ---

Inclusion: Registration: - Pathological diagnosis of adenocarcinoma of the lung carrying common EGFR activating mutations associated with EGFR-TKI sensitivity (Del19 or L858R); performed locally; no other EGFR mutations will be allowed. --- L858R ---

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 ---

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 ---

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 ---

Currently, whether adjuvant therapy should be applied to Stage Ib non-small cell lung cancer (NSCLC) patients who received radical resection remains controversial. There is still no clear evidence that the postoperative adjuvant chemotherapy or other treatments can improve the survival rate for patients with stage Ib NSCLC. Tyrosine Kinase Inhibitors (TKIs) such as Gefitinib and Erlotinib are widely accepted as the first-line therapy for Epidermal growth factor receptor (EGFR) gene mutation late stage NSCLC patients. However the effect is largely uncertain for early stage patients who received surgery. The investigators aim to evaluate the effect of postoperative adjuvant use of Gefitinib for high risk stage Ib EGFR sensitive mutation NSCLC patients.

NCT02526537

Conditions

1. NSCLC

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

2. Patients with pathology confirmed Ib stage NSCLC 3. Patients with deletion of exon 19 or mutation of L858R at exon 21 in EGFR gene 4. ECOG score of 0-1 5. Life expectancy over 12 weeks 6. --- L858R ---

The purpose of this study was to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.

NCT02468661

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: INC280 single agent
2. Drug: erlotinib

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

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

Composite pharmacokinetics of erlotinib in the presence of INC280.. Inclusion Criteria: - Locally advanced or metastatic NSCLC - EGFR mutation (L858R and /or ex19del) - cMET amplification by FISH (GCN ≥ 6), - Acquired resistance to EGFR TKI (1st or 2nd generation) - ECOG performance status (PS) ≤ 1. Exclusion Criteria: - Prior treatment with 3rd generation TKI - PhaseII : Prior treatment with any of the following agents: - Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor. --- L858R ---

- Platinum-based chemotherapy as first line treatment Inclusion Criteria: - Locally advanced or metastatic NSCLC - EGFR mutation (L858R and /or ex19del) - cMET amplification by FISH (GCN ≥ 6), - Acquired resistance to EGFR TKI (1st or 2nd generation) - ECOG performance status (PS) ≤ 1. Exclusion Criteria: - Prior treatment with 3rd generation TKI - PhaseII : Prior treatment with any of the following agents: - Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor. --- L858R ---

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 ---

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 ---

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 ---

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 ---

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 ---

- 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 ---

The development of biomarkers will lead the dynamic of personalized medicine and fill the unsatisfied needs in oncology for prediction of therapeutic response. Molecular imaging enables non invasive quantification of biomarkers. The development of molecular imaging biomarkers is closely related to the development of therapeutic molecules. Among the potential targets, kinases offer a lot of advantages: (i) they play a central role in cellular regulation, (ii) numerous kinase-specific small molecule libraries exist in biotech and pharma industry, (iii) several kinase-targeted therapies are used in clinic (imatinib, sorafenib, sunitinib…) with application across a variety of therapeutic indications. Among the imaging technologies, the Positron Emission Tomography (PET) is the most sensitive and dedicated to evaluate small molecules. However few radiotracers are available and their specificity limits their clinical use. The IMAkinib® approach is an innovative method proposed to develop new PET radiotracers adapted to current medical and economical challenges. The epidermal growth factor receptor (EGFR) is an established target for the treatment of advanced non-small cell lung cancer (NSCLC). The EGFR tyrosine kinase inhibitors (TKIs) Gefitinib (Iressa®), erlotinib (Tarceva®) and afatinib (Giotrif®) have already been approved for treatment of NSCLC harboring EGFR activating mutations (L858R or del exon 19). Unfortunately the majority of patients will develop a resistance to the TKI in the long term (6-12 months). If the mechanism of resistance is not yet fully characterized, most patients (50%) will acquire an additional T790M mutation of EGFR. TKI PET-imaging can provide a tool to determine and predict responsiveness to EGFR TKI in vivo. That is why, the investigators have selected and radiolabeled (18-Fluor) a compound targeting specifically EGFR mutated ([18F]-ODS2004436) which was further evaluated in a preclinical imaging study to determine the feasibility of TKI-PET. The investigators proved in vivo that [18F]-ODS2004436 a compound is a good candidate to evaluate the EGFR activity in human lung tumours using PET imaging.

NCT02847377

Conditions

1. Carcinoma, Non-Small-Cell Lung

Interventions

1. Other: Injection of [18F]-ODS2004436 radiotracer

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

The EGFR tyrosine kinase inhibitors (TKIs) Gefitinib (Iressa®), erlotinib (Tarceva®) and afatinib (Giotrif®) have already been approved for treatment of NSCLC harboring EGFR activating mutations (L858R or del exon 19). --- L858R ---

The investigators will examine efficacy and toxicity of gefitinib in Korean patients with EGFR wild tumors diagnosed with direct sequence test.

NCT01312337

Conditions

1. Nonsmall Cell Lung Cancer

Interventions

1. Drug: salvage iressa

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

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

Inclusion Criteria: - Pathologically proven NSCLC - Ineligibile for curative treatment (namely, stage IIIb or IV) - History of one to three prior systemic chemotherapy tumors without active EGFR mutations (exon 19 deletion, L858R mutation in exon 21) - At least one lesion that was unidimensionally measurable by computed tomography (by RECIST 1.1) - 18 years old or older - Performance status ECOG 0-2 - Adequate organ function as evidenced by the following: - Absolute neutrophil count > 1.0 x 109/L - Platelets > 75 x 109/L - Total bilirubin ≤ 1.5 UNL - AST and/or ALT < 5 UNL - Creatinine clearance ≥ 45mL/min Exclusion Criteria: - Previous EGFR TKI therapy history - Systemic anticancer therapy within the previous 3 weeks - Other invasive malignancy within the past 2 years except non-melanoma skin cancer, in situ cervix cancer, or papillary thyroid cancer - Other concurrent illness that would preclude study participation (severe heart disease) - Other concurrent physical condition (e.g., infectious disease) that would preclude study participation - Pregnant or nursing Inclusion Criteria: - Pathologically proven NSCLC - Ineligibile for curative treatment (namely, stage IIIb or IV) - History of one to three prior systemic chemotherapy tumors without active EGFR mutations (exon 19 deletion, L858R mutation in exon 21) - At least one lesion that was unidimensionally measurable by computed tomography (by RECIST 1.1) - 18 years old or older - Performance status ECOG 0-2 - Adequate organ function as evidenced by the following: - Absolute neutrophil count > 1.0 x 109/L - Platelets > 75 x 109/L - Total bilirubin ≤ 1.5 UNL - AST and/or ALT < 5 UNL - Creatinine clearance ≥ 45mL/min Exclusion Criteria: - Previous EGFR TKI therapy history - Systemic anticancer therapy within the previous 3 weeks - Other invasive malignancy within the past 2 years except non-melanoma skin cancer, in situ cervix cancer, or papillary thyroid cancer - Other concurrent illness that would preclude study participation (severe heart disease) - Other concurrent physical condition (e.g., infectious disease) that would preclude study participation - Pregnant or nursing Nonsmall Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- L858R ---

Inclusion Criteria: - Pathologically proven NSCLC - Ineligibile for curative treatment (namely, stage IIIb or IV) - History of one to three prior systemic chemotherapy tumors without active EGFR mutations (exon 19 deletion, L858R mutation in exon 21) - At least one lesion that was unidimensionally measurable by computed tomography (by RECIST 1.1) - 18 years old or older - Performance status ECOG 0-2 - Adequate organ function as evidenced by the following: - Absolute neutrophil count > 1.0 x 109/L - Platelets > 75 x 109/L - Total bilirubin ≤ 1.5 UNL - AST and/or ALT < 5 UNL - Creatinine clearance ≥ 45mL/min Exclusion Criteria: - Previous EGFR TKI therapy history - Systemic anticancer therapy within the previous 3 weeks - Other invasive malignancy within the past 2 years except non-melanoma skin cancer, in situ cervix cancer, or papillary thyroid cancer - Other concurrent illness that would preclude study participation (severe heart disease) - Other concurrent physical condition (e.g., infectious disease) that would preclude study participation - Pregnant or nursing Inclusion Criteria: - Pathologically proven NSCLC - Ineligibile for curative treatment (namely, stage IIIb or IV) - History of one to three prior systemic chemotherapy tumors without active EGFR mutations (exon 19 deletion, L858R mutation in exon 21) - At least one lesion that was unidimensionally measurable by computed tomography (by RECIST 1.1) - 18 years old or older - Performance status ECOG 0-2 - Adequate organ function as evidenced by the following: - Absolute neutrophil count > 1.0 x 109/L - Platelets > 75 x 109/L - Total bilirubin ≤ 1.5 UNL - AST and/or ALT < 5 UNL - Creatinine clearance ≥ 45mL/min Exclusion Criteria: - Previous EGFR TKI therapy history - Systemic anticancer therapy within the previous 3 weeks - Other invasive malignancy within the past 2 years except non-melanoma skin cancer, in situ cervix cancer, or papillary thyroid cancer - Other concurrent illness that would preclude study participation (severe heart disease) - Other concurrent physical condition (e.g., infectious disease) that would preclude study participation - Pregnant or nursing Nonsmall Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- L858R --- --- L858R ---

This open-label, single arm study will evaluate the safety and efficacy of Tarceva (erlotinib) as first-line therapy in participants with stage IV or recurrent non-small cell lung cancer who harbour epidermal growth factor receptor (EGFR) mutations. All participants will receive Tarceva 150 mg daily orally until disease progression or unacceptable toxicity occurs. At the investigator's discretion, participants may receive Tarceva beyond disease progression.

NCT01310036

Conditions

1. Non-Squamous Non-Small Cell Lung Cancer

Interventions

1. Drug: Erlotinib

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

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

PFS2 was defined as time from first study dose to off-erlotinib progressive disease (PD), assessed by the investigator based on overall clinical evaluation.. Objective Response Rate (ORR) for All Participants and Participants With EGFR Mutation E19del or L858R. --- L858R ---

PR was defined as least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.. Disease Control Rate (DCR) for All Participants and Participants With EGFR Mutation E19del or L858R. --- L858R ---

PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions.. Progression-free Survival for Participants With EGFR Mutation E19del or L858R Per RECIST, v. 1.1 (PFS1). --- L858R ---

PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions.. Overall Survival (OS) for All Participants and Participants With EGFR Mutation E19del or L858R. --- L858R ---

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 ---

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 ---

1. To compare EGFR mutations between primary non-small cell lung cancer (NSCLC) tumours and corresponding CTCs isolated by a label-free microfluidic device-based system 2. To characterize the association between clinical response in NSCLC patients treated with gefitinib and serial changes in CTC EGFR mutations detected by a label-free microfluidic device-based system The investigators recently developed a label-free, microfluidic device for capturing circulating tumour cells (CTCs) and acquired a Fluidigm Biomark digital PCR instrument for reliable low-level DNA quantification. The overall aim of this study is to test the feasibility of using these state-of-the-art devices to reliably detect clinically relevant EGFR mutations in CTCs.

NCT01193829

Conditions

1. Patients With Non-small Cell Lung Cancer

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

DNA will be extracted from the retrieved CTCs and tumour samples, and analyzed exon 19 deletion, L858R and T790M mutations by digital PCR on the Fluidigm Biomark according to methods described previously.23 --- L858R ---

This is a Phase 2 study to evaluate the efficacy and the safety/ tolerability of Almonertinib in NSCLC patients with uncommon EGFR Mutation or EGFR exon 20 insertion mutations. Patients with EGFR exon 20 insertion mutations have to had at least one prior systemic treatment for locally advanced or metastatic NSCLC.

NCT04553887

Conditions

1. Non Small Cell Lung Cancer

Interventions

1. Drug: Almonertinib

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

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

Inclusion Criteria: 1. 18-75years#ECOG PS#0-2#Life expectancy of more than 3 months#with measurable lesion ( RECIST1.1). 2. Cohort A: Patients with EGFR exon 20 insertion, failure of first-line standard chemotherapy, or intolerance to chemotherapy Cohort B: Patients with uncommen EGFR mutations but without exon 19 deletion, L858R, T790M, and exon 20 insertion 3. ≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction#Previously received radiation therapy, but the radiotherapy area must be <25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment. --- L858R ---

The currently approved TKIs (ie, erlotinib, gefitinib, afatinib, osimertinib) are not considered to be exon 20 insertion-selective and are permissible 1. Patients with EGFR 19 exon deletion mutation, 21 exon L858R mutation or 20 exon T790M mutation. --- L858R ---

Judgment by the investigator that should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements Inclusion Criteria: 1. 18-75years#ECOG PS#0-2#Life expectancy of more than 3 months#with measurable lesion ( RECIST1.1). 2. Cohort A: Patients with EGFR exon 20 insertion, failure of first-line standard chemotherapy, or intolerance to chemotherapy Cohort B: Patients with uncommen EGFR mutations but without exon 19 deletion, L858R, T790M, and exon 20 insertion 3. ≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction#Previously received radiation therapy, but the radiotherapy area must be <25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment. --- L858R ---

The study purpose is to evaluate the safety, tolerability, and preliminary efficacy of the addition of INC280, trametinib, ribociclib, gefitinib, or LXH254 to EGF816 in adult patients with advanced EGFR-mutant NSCLC.

NCT03333343

Conditions

1. EGFR-mutant Non-small Cell Lung Cancer

Interventions

1. Drug: EGF816
2. Drug: trametinib
3. Drug: ribociclib
4. Drug: LXH254
5. Drug: INC280
6. Drug: gefitinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Inclusion Criteria: - Patients must have histologically or cytologically confirmed locally advanced (stage IIIB) or metastatic (stage IV) EGFR mutant (ex19del, L858R) NSCLC. --- L858R ---

- Requirements of EGFR mutation status and prior lines of treatment: - Treatment naive patients, who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation (e.g., L858R and/or ex19del), have not received any systemic antineoplastic therapy for advanced NSCLC and are eligible to receive EGFR TKI treatment. --- L858R ---

- Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation AND an acquired T790M mutation (e.g., L858R and/or ex19del, T790M+) following progression on prior treatment with a 1st-generation EGFR TKI or 2nd-generation EGFR TKI. --- T790M --- --- L858R ---

- Patients who have been treated with systemic anti-neoplastic therapy within: - 2 weeks for fluoropyrimidine monotherapy - 6 weeks for nitrosoureas and mitomycin - 4 weeks or ≤ 5 half-lives (whichever is shorter) for biological therapy (including monoclonal antibodies) and continuous or intermittent small molecule therapeutics or any other investigational agent Inclusion Criteria: - Patients must have histologically or cytologically confirmed locally advanced (stage IIIB) or metastatic (stage IV) EGFR mutant (ex19del, L858R) NSCLC. --- L858R ---

This is a phase Ib study to evaluate safety and tolerability of dual checkpoint inhibition (DCI) of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) with SBRT in the treatment of oligometastatic NSCLC. This study will examine the sequential delivery of SBRT to all disease sites followed by combination of durvalumab and tremelimumab for patients for whom the goal is ablating all known sites of disease. The investigators anticipate that for many participants this will be the first line-therapy. Participants who have received prior-platinum-based chemotherapy and/or any line of prior chemotherapy are eligible. Prior immunotherapy treatment is not allowed.

NCT03275597

Conditions

1. Non-small Cell Lung Cancer
2. Non-small Cell Lung C
3. Non-small Cell Lung Cancer Stage IV

Interventions

1. Drug: Durvalumab
2. Drug: Tremelimumab
3. Radiation: Stereotactic Body Radiotherapy

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

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

exon 19 deletion or exon 21 L858R) or ALK rearrangement. --- L858R ---

This study will compare the effectiveness of osimertinib alone with the combination of osimertinib and chemotherapy (carboplatin and pemetrexed) in people with metastatic lung cancer that has a change (mutation) in the gene EGFR. Osimertinib alone is the usual treatment for metastatic EGFR-mutant lung cancer. Researchers think adding chemotherapy to osimertinib could possibly add to the anticancer effects of the usual treatment and help stop cancer from growing or spreading.

NCT04410796

Conditions

1. Metastatic Non-small Cell Lung Cancer

Interventions

1. Drug: Osimertinib
2. Drug: Carboplatin
3. Drug: Pemetrexed

MeSH:Lung Neoplasms

HPO:Neoplasm of the lung

Patients will be seen on C1D1 for osimertinib start (telemedicine visits for C1D1 assessments are acceptable) Randomization/treatment portion: Patients will be randomized to continue osimertinib alone (Arm A) or addition of carboplatin/pemetrexed chemotherapy to osimertinib (Arm B).Randomization will be accomplished by the method of random permuted block and patients will be stratified by type of EGFR mutation (EGFR exon 19/EGFR L858R or other) and presence of CNS metastases (absent, present). --- L858R ---

This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status of 2-3).

NCT03191786

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
2. Drug: Vinorelbine
3. Drug: Gemcitabine

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

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

Investigator-assessed PFS according to RECIST v1.1 will be assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay.. Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition - No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected - No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition - Life expectancy greater than or equal to (>/=) 8 weeks - Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). --- L858R ---

Grade 3 or higher toxicities due to any prior therapy (example [e.g.], radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication - Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy General Medical Exclusion Criteria: - History of autoimmune disease except autoimmune-related hypothyroidism and controlled Type I diabetes mellitus - History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis - Known positivity for human immunodeficiency virus (HIV) - Known active hepatitis B or hepatitis C - Active tuberculosis - Severe infections within 4 weeks prior to randomization - Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina - Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study - Prior allogeneic bone marrow transplantation or solid organ transplant - Participants with an illness or condition that may interfere with capacity or compliance with the study protocol, as per investigator's judgment - Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization Exclusion Criteria Related to Atezolizumab: - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation - Oral or IV antibiotic treatment - Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study - Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies - Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to randomization - Treatment with systemic corticosteroids or other immunosuppressive medications - Participants not willing to stop treatment with traditional herbal medicines Exclusion Criteria Related to Chemotherapy: - Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is [i.e.] vinorelbine, oral or intravenous, and gemcitabine, intravenous) Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition - No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected - No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition - Life expectancy greater than or equal to (>/=) 8 weeks - Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). --- L858R ---

This study is a prospective, multicenter, real-world study to investigate the efficacy and safety of bevacizumab plus epidermal growth factor (EGFR) Tyrosine Kinase Inhibitors in Chinese Patients With Stage IIIB/IV EGFR-mutant Non-small Cell Lung Cancer.

NCT04575415

Conditions

1. NSCLC

Interventions

1. Drug: Bevacizumab
2. Drug: Erlotinib
3. Drug: Gefitinib
4. Drug: Icotinib
5. Drug: Afatinib
6. Drug: Dacomitinib
7. Drug: Osimertinib

An exon 19 deletion mutation or exon 21 L858R mutation in EGFR has been found clinically, with or without EGFR T790M mutation 5. Eastern Cooperative Oncology Group performance status 0-2 or KPS ≥60 6. --- L858R ---

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 ---

This research study is studying a drug intervention as a possible treatment for lung cancer. The drugs involved in this study are: - Nivolumab - Carboplatin - Pemetrexed - Ipilimumab

NCT03256136

Conditions

1. Lung Cancer

Interventions

1. Drug: Carboplatin
2. Drug: Nivolumab
3. Drug: pemetrexed
4. Drug: Ipilimumab

MeSH:Lung Neoplasms

HPO:Neoplasm of the lung

- EGFR-mutant NSCLC: EGFR activating gene mutation (e.g., L858R, exon 19 deletion) as well as a T790M mutation per local testing. --- L858R ---

Currently the investigators have two different classes of second-line treatment options in recurrent non-small Cell Lung Cancer (NSCLC). In chemotherapy, docetaxel and pemetrexed produced similar treatment efficacy outcomes, while pemetrexed had a better tolerability. In recent analysis of pemetrexed clinical studies, a strong treatment-by-histology interaction in overall survival and progression free survival that indicated better efficacy for non-squamous patients treated with pemetrexed. These data supports that pemetrexed could be a preferable chemotherapy drug especially in adenocarcinoma NSCLC patients.

NCT00903292

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: erlotinib (Tarceva)
2. Drug: pemetrexed (Alimta)

MeSH:Adenocarcinoma Adenocarcinoma of Lung

Since typical EGFR gene mutations (i.e., the deletion of typically five amino acids at codons 746-750 (ELREA) in exon 19 and a leucine-to-arginine mutation at codon 858 (L858R)) are a good predictor for tumor response to tyrosine kinase inhibitor, this present study is to tailor the patient's treatment according to his/her EGFR gene mutation status. --- L858R ---

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 ---

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 ---

- 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 ---

- 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 ---

This study will be performed as a local multicenter, randomized, phase III clinical study. It will compare the adjuvant chemotherapy in Stage IB-IIIA NSCLC with common EGFR mutation (Exon 19 deletion or L858R) who underwent total resection and the Erlotinib-Intercalation adjuvant chemotherapy with the chemotherapy alone. The patients will be randomly assigned to the Intercalation combination chemotherapy regimen and the chemotherapy alone regimen at the ratio of 1:1. The treatment regimen of each arm is as follows.

NCT02795884

Conditions

1. NSCLC

Interventions

1. Drug: intercalation therapy using pemetrexed, cisplatin and erlotinib
2. Drug: Vinorelbine, cisplatin

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

It will compare the adjuvant chemotherapy in Stage IB-IIIA NSCLC with common EGFR mutation (Exon 19 deletion or L858R) who underwent total resection and the Erlotinib-Intercalation adjuvant chemotherapy with the chemotherapy alone. --- L858R ---

- Stage IB-IIIA Non-squamous NSCLC (Based on AJCC Version 7 TNM Disease Stages) - Surgically complete resection - Confirmed with Exon 19 deletion or L858R EGFR mutation - Complete recovery from the surgery. --- L858R ---

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 ---

- 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 ---

This randomized phase III trial is studying gefitinib and synchronous pemetrexed/cisplatin chenmotherapy to see how well it works compared to pemetrexed/cisplatin chenmotherapy alone in treating patients who have undergone surgery for stage II-IIIA(N1-N2) lung adenocarcinoma with EGFR activating mutation in Asian population.

NCT02518802

Conditions

1. Lung Neoplasms

Interventions

1. Drug: Gefitinib
2. Drug: Pemetrexed

MeSH:Adenocarcinoma Lung Neoplasms Adenocarcinoma of Lung

HPO:Neoplasm of the lung

- Target population is completely resected pathological stage II-IIIA(N1-N2) NSCLC with EGFR exon 19 deletions and exon 21 L858R activating mutation. --- L858R ---

To assess the efficacy and safety of AZD9291 versus Placebo, in patients with Epidermal Growth Factor Receptor Mutation Positive stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy

NCT02511106

Conditions

1. Stage IB-IIIA Non-small Cell Lung Carcinoma

Interventions

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

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

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

5. Confirmation by the central laboratory that the tumour 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 including T790M. --- L858R ---

Stage IB-IIIA Non-small Cell Lung Carcinoma Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy and safety of AZD9291 versus placebo in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) with centrally confirmed, most common sensitising EGFR mutations (Ex19Del and L858R) either alone or in combination with other EGFR mutations as confirmed by a central test, who have had complete tumour resection, with or without postoperative adjuvant chemotherapy. --- L858R ---

Continuous treatment until progression or occurence of intolerable Adverse Event (AE) or end of trial. The end of trial is one year after the last patient has entered the study.

NCT02514174

Conditions

1. Carcinoma, Non-Small-Cell Lung
2. ErbB Receptors

Interventions

1. Drug: Afatinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

A Single Arm Phase IV Study of Afatinib in Elderly Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer Whose Tumors Have Epidermal Growth Factor Receptor (EGFR) Exon 19 Deletions or Exon 21(L858R) Substitution Mutations. --- L858R ---

Staging is based on American Joint Committee on Cancer (AJCC) Staging for NSCLC 7th edition (R12-4710) - Evidence of common EGFR mutation (Del 19 and/or L858R) - Age >= 70 years - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (R01-0787) - Further inclusion criteria apply. --- L858R ---

This phase I trial studies the side effects and best dose of sapanisertib when given together with osimertinib in treating patients with stage IV EGFR mutation positive non-small cell lung cancer that has progressed after treatment with an EGFR tyrosine kinase inhibitor. Sapanisertib and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT02503722

Conditions

1. Metastatic Lung Non-Small Cell Carcinoma
2. Recurrent Lung 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. Other: Laboratory Biomarker Analysis
2. Drug: Osimertinib
3. Other: Pharmacological Study
4. Drug: Sapanisertib

MeSH:Carcinoma Carcinoma, Non-Small-Cell Lung

HPO:Carcinoma Non-small cell lung carcinoma

Descriptive statistics and plotting of data will also be used to better understand potential relationships.. Inclusion Criteria: - Patients with stage IV or recurrent/metastatic histologically or cytologically confirmed non-squamous NSCLC - NSCLC must harbor an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion) - Progressive disease on osimertinib (AZD9291) given first line - For the dose expansion portion ONLY, patient must: 1) have progression of disease with first line osimertinib administered for advanced or metastatic disease as the last previous systemic treatment, 2) be treatment naïve for other 3rd generation EGFR-TKI (CO-1686) and mTOR inhibitors - Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension >= 10 mm (>= 1 cm) by computed tomography (CT) imaging or magnetic resonance imaging (MRI) within 28 days prior to start of protocol therapy; the CT from a combined positron emission tomography (PET)/CT may be used if it is of diagnostic quality; laboratory parameters are not acceptable as the only evidence of disease - For the dose expansion, no other systemic therapies for advanced/metastatic disease is permissible after first line osimertinib - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) - Patients with a prior history of brain metastases are eligible provided: - The brain metastases have been treated; patients with small brain metastases for which radiation or surgery is not indicated, may be eligible on discussion with the study chair. --- L858R ---

medically significant (symptomatic) bradycardia, complete left bundle branch block, third degree heart block and second-degree heart block or history of arrhythmia requiring an implantable cardiac defibrillator; or within the last 6 months before administration of the first dose of drug: - Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) - Placement of a pacemaker for control of rhythm - Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures - Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures - New York Heart Association (NYHA) class III or IV heart failure - Symptomatic pulmonary embolism or asymptomatic pulmonary emboli within the last 3 months - Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTcF >= 470 msec (mean value) obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value, or history of congenital long QT syndrome, or torsades de pointes); any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval - Left ventricular ejection fraction (LVEF) by either multigated acquisition (MUGA) or echocardiography (ECHO) less than lower limit of normal - Patients with active malignancies other than NSCLC or prior curatively treated malignancy at high risk of relapse during the study period with the exception of localized squamous or basal cell skin cancers - Concurrent anti-cancer therapy - History of hypersensitivity attributed to compounds of similar chemical or biologic composition to MLN0128 (TAK-228) or osimertinib (AZD9291) - Pregnant women or women who are breast feeding are not eligible for the study; the effects of MLN0128 (TAK-228) and osimertinib (AZD9291) on the developing human fetus are unknown - Women of non-child bearing potential must be: - Women more than 50 years must be post-menopausal for at least 12 months following the end of all exogenous hormonal treatments OR - Women under 50 years must be postmenopausal for at least 12 months following the end of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution OR - Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation - Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days of registration and must agree to: - Practice 1 highly effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 120 days (or longer, as mandated by local labeling [e.g., United Surgical Partners International (USPI), Summary of Product Characteristics (SmPC), etc.;]) after the last dose of study drug, OR - Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient; NOTE: Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception; female and male condoms should not be used together - Male patients, even if surgically sterilized (i.e., status postvasectomy) must agree to: - Practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR - Practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient; NOTE: Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception; female and male condoms should not be used together - Not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug - Inability to discontinue drugs that are strong cytochrome P450 3A4 (CYP3A4) or P450 3A5 (CYP3A5), cytochrome P450 2C19 (CYP2C19), and cytochrome P450 2C9 (CYP 2C9) inhibitors and/or inducers; and substrates of CYP 3A4/5 or CYP1A2 that are sensitive or have a narrow therapeutic window at least three weeks prior to study registration - Patients receiving systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study drug - Consumption of grapefruit or grapefruit juice is not permitted during the study; patients should not consume food or beverages containing the fruit or juice of grapefruits or Seville oranges within 7 days before the first dose of study drug and throughout the study - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MLN0128 (TAK-228) and osimertinib (AZD9291) - No concomitant use of proton pump inhibitors (PPI) is allowed; any prior PPI must be discontinued at least one week before receiving MLN0128 (TAK-228) Inclusion Criteria: - Patients with stage IV or recurrent/metastatic histologically or cytologically confirmed non-squamous NSCLC - NSCLC must harbor an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion) - Progressive disease on osimertinib (AZD9291) given first line - For the dose expansion portion ONLY, patient must: 1) have progression of disease with first line osimertinib administered for advanced or metastatic disease as the last previous systemic treatment, 2) be treatment naïve for other 3rd generation EGFR-TKI (CO-1686) and mTOR inhibitors - Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension >= 10 mm (>= 1 cm) by computed tomography (CT) imaging or magnetic resonance imaging (MRI) within 28 days prior to start of protocol therapy; the CT from a combined positron emission tomography (PET)/CT may be used if it is of diagnostic quality; laboratory parameters are not acceptable as the only evidence of disease - For the dose expansion, no other systemic therapies for advanced/metastatic disease is permissible after first line osimertinib - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) - Patients with a prior history of brain metastases are eligible provided: - The brain metastases have been treated; patients with small brain metastases for which radiation or surgery is not indicated, may be eligible on discussion with the study chair. --- L858R ---

To compare the overall survival of NSCLC patients receiving 2nd- or 3rd-line systemic therapy with docetaxel + plinabulin (DP Arm) to patients treated with docetaxel + placebo (D5W) (D Arm) for advanced or metastatic disease. Secondary purposes of the study are: - To compare the neutropenia (incidence of Grade 4 neutropenia [absolute neutrophil count (ANC) < 0.5 × 10^9/L]) on Day 8 (+/- 1 day) of Cycle 1), DoR, neutrophil count on Day 8 (+/- 1 day) of Cycle 1, incidence of docetaxel dose reduction and/or docetaxel dose withheld in Cycle 2 due to neutropenia in Cycle 1, QoL (EORTC QLQ-C30 [item 30, average overall quality of life over all observable weeks]), ORR, and PFS in patients with NSCLC treated in the DP Arm to patients treated in the D Arm as 2nd- or 3rd-line therapy for advanced or metastatic disease. - To compare the safety and adverse events profile of the DP Arm to D Arm. - To compare dose intensity of docetaxel (percent dose administered compared to dose assigned) between the 2 treatment arms. - To evaluate population pharmacokinetics in patients enrolled in China and rest of world (RoW).

NCT02504489

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Drug: Docetaxel + Plinabulin (DP)
2. Drug: Docetaxel (D)

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

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

Radiographic tumor assessment is to be performed within 28 days prior to randomization. 5. patients with nonsquamous NSCLC must have been tested for EGFR exon 19 deletion and Exon 21 L858R substitution mutation. --- L858R ---

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 ---

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 ---

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 ---

To evaluate the efficacy and toxicity of patients treated with hypofractionated radiotherapy for limited metastatic NSCLC harboring sensitizing EGFR mutations after first line TKI therapy. An exploratory biomarker analysis in blood and tumor samples is also planned.

NCT02788058

Conditions

1. Lung Adenocarcinoma
2. EGFR Positive Non-small Cell Lung Cancer

Interventions

1. Drug: EGFR-TKI
2. Radiation: Thoracic Hypofractionated Radiotherapy

MeSH:Adenocarcinoma Adenocarcinoma of Lung

Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma harboring sensitizing EGFR mutations (L858R, exon 19 deletion), and became oligometastatic disease after 3 months TKI, evaluated by PET/CT scan, brain MRI, and abdomen ultrasound (≤6 discrete lesions of disease, exclusive of the brain metastases, ≤3 lesions in the liver, ≤3 lesions in the lung); - All sites of disease must be amenable to definitive RT; - An intrathoracic lymph nodal station is considered 1 discrete lesion, according to IASLC lymph nodal station map; - Age 18 years or older; - ECOG Performance Status 0-2; - Adequate bone marrow, liver and renal function, as specified below: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L; Hemoglobin ≥ 8 g/dL; Platelets ≥ 100 x 109/L; Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) ; AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present; Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal; - For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment; - Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter; - Patients and their family signed the informed consents; Exclusion Criteria: - Received chemotherapy before TKI therapy; - Brain parenchyma or leptomeningeal disease; - Any site of disease that is not amenable to definitive RT; - Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment; - Any medical co-morbidities that would preclude radiation therapy. --- L858R ---

The investigators postulated that the exploitation of the pro-immunogenic effects of radiotherapy with thymosin might result in abscopal responses among patients with metastatic cancer. The research is designed to evaluate the efficacy and toxicity of patients treated with hypofractionated radiotherapy combined with thymosin alpha 1. An exploratory biomarker analysis in blood and tumor samples is also planned.

NCT02787447

Conditions

1. Lung Adenocarcinoma

Interventions

1. Drug: TKI
2. Radiation: Thoracic Hypofractionated Radiotherapy
3. Drug: Thymosin Alpha 1

MeSH:Adenocarcinoma Adenocarcinoma of Lung

Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma harboring sensitizing EGFR mutations (L858R, exon 19 deletion), and showed stable disease after 3 months TKI, evaluated twice by PET/CT scan, brain MRI, and abdomen ultrasound (≥3 measurable lesions, and these lesions haven't received local therapy) - Age 18 years or older - ECOG Performance Status 0-2 - Adequate bone marrow, liver and renal function, as specified below: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L; Hemoglobin ≥ 8 g/dL; Platelets ≥ 100 x 109/L; Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) ; AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present; Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal - For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment - Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter - Patients and their family signed the informed consents Exclusion Criteria: - Received chemotherapy before TKI therapy - Brain parenchyma or leptomeningeal disease - Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment - Any medical co-morbidities that would preclude radiation therapy. --- L858R ---

This is a single arm phase II clinical trial, which aims to evaluate the effectiveness of combination of gefitinib and doublet chemotherapy or antiangiogenesis in advanced non-small cell lung cancer patients with EGFR activating mutation, accompanied with Bim deletion or low activating EGFR mutation abundance.

NCT02930954

Conditions

1. Non-small-cell Lung Cancer

Interventions

1. Drug: Gefitinib
2. Drug: pemetrexed or gemcitabine plus carboplatin,
3. Drug: bevacizumab

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

Inclusion Criteria: - Histologically documented, locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer, anti-cancer treatment naiive - EGFR exon 19 deletion or exon 21 L858R. --- L858R ---

- Bim deletion by realtime PCR, or low abundance for EGFR mutation, for 19Del less than 4.9%, for L858R less than 9.5%. --- L858R ---

- Unhealed bone fracture or wound for long time Inclusion Criteria: - Histologically documented, locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer, anti-cancer treatment naiive - EGFR exon 19 deletion or exon 21 L858R. --- L858R ---

This single arm, open-label study will evaluate the efficacy and safety of erlotinib (Tarceva) in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.

NCT01260181

Conditions

1. Non-Squamous Non-Small Cell Lung Cancer

Interventions

1. Drug: Erlotinib

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

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

Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21.. Median Time Taken From the First Response Until Disease Progression Based on RECIST v 1.1 as Determined by the Investigator. --- L858R ---

The purpose of the study is to learn whether the study drug (capmatinib) helps to control lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe when given to patients suffering from a particular type of lung cancer. This type of cancer is called non-small cell lung cancer (NSCLC) with certain specific genetic alterations (called mutations) of a gene called MET, within a specific part of the gene called exon 14. Approximately 90 people with advanced or metastatic lung cancer, with these specific mutations in the MET gene but without changes in their epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes, will be enrolled in this study. The study drug, capmatinib (also known as INC280), is an oral drug that is called a 'targeted' medicine, which means it targets particular processes that may not be working properly in cancer cells (called dysregulation). The dysregulation of the MET signaling in cancer cells of patients with NSCLC is believed to make the cancer worse. Capmatinib has been shown to selectively block the effects of the MET gene and therefore may help in keeping the disease under control, stopping cancer cells from growing. Docetaxel is a standard chemotherapy medicine commonly used to treat your type of lung cancer. This standard, anti-cancer medicine is a cytotoxic chemotherapy. The reason for this study is to find out if capmatinib can control lung cancer better. Patients will be randomly assigned to get either capmatinib or docetaxel in a 2 to 1 ratio: - Capmatinib: 2 out of 3 possibility or 66% chance of getting this treatment, - Docetaxel: 1 out of 3 possibility or 33% chance of getting this treatment. During treatment, visits will be scheduled every 21 days.

NCT04427072

Conditions

1. Carcinoma, Non-Small-Cell Lung

Interventions

1. Drug: Capmatinib
2. Drug: Docetaxel

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

The EGFR wt status (for EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations. --- L858R ---

A Phase II, open label, non-randomized, multiple-arm, single-center clinical trial in patients with advanced rare solid tumors who failed to standard treatment.

NCT04423185

Conditions

1. Rare Tumor

Interventions

1. Drug: Almonertinib 110 MG
2. Drug: Dacomitinib 45 MG
3. Drug: Alectinib 150 MG
4. Drug: Crizotinib 250 MG
5. Drug: Pyrotinib 160/80 MG
6. Drug: Imatinib 400 MG
7. Drug: Niraparib 200/300 MG
8. Drug: Palbociclib 125mg
9. Drug: Vemurafenib 240 MG
10. Drug: Sintilimab 100MG
11. Drug: Atezolizumab 1680 MG

MeSH:Neoplasms

HPO:Neoplasm

Patients with advanced rare tumors who failed to standardized treatment carrying actionable alterations as "EGFR mutation (exon 19 deletion mutation, L858R replacement mutation), ALK gene fusion, ROS-1 gene fusion, C-MET gene amplification or mutation (D1010 mutation, 14 exon mutation, y1003 mutation), BRAF mutation, CDKN2A mutation, BRCA1/2 mutation, HER-2 mutation, HER-2 over expression/amplification, C-KIT mutation", will enroll targeted therapy arms and be given corresponding targeted drugs (Dacomitinib, Crizotinib). --- L858R ---

To compare the efficacy and safety of gefitinib combined with bevacizumab and gefitinib in the treatment of L858R positive mutation in exon 21 of EGFR gene in advanced NSCLC.

NCT04425187

Conditions

1. PFS

Interventions

1. Drug: Gefitinib
2. Drug: Bevacizumab Combined With Gefitinib

Bevacizumab Combined With Gefitinib in the Treatment of Advanced NSCLC Clinical Study of L858R Positive Mutation Patients. --- L858R ---

Bevacizumab Combined With Gefitinib in the Treatment of Advanced NSCLC To compare the efficacy and safety of gefitinib combined with bevacizumab and gefitinib in the treatment of L858R positive mutation in exon 21 of EGFR gene in advanced NSCLC. --- L858R ---

The PFS of gefitinib combined with bevacizumab and gefitinib alone were compared in patients with L858R mutation in exon 21 of EGFR gene in stage IIIB-IV local advanced, recurrent or metastatic NSCLC.. Inclusion Criteria: 1. Age ≥ 18 years old, gender unlimited. --- L858R ---

4. According to the method of second-generation sequencing, L858R point mutation in exon 21 of EGFR gene was found in primary NSCLC with or without any other coexisting mutations. --- L858R ---

This will be a Phase II, open-label, single-arm, multicenter study of the efficacy and safety of osimertinib (80 mg orally once daily) in patients with LM associated with EGFRm+ NSCLC.

NCT04563871

Conditions

1. Non-small Cell Lung Cancer (NSCLC)

Interventions

1. Drug: 80mg Osimertinib

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

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

3. Male and female patients must be at least 18 years of age. 4. Patients must have documented (only allowed for EGFRm+ [exon 19 deletions or L858R] in pre-treated patients) and/or confirmed central/local test result showing eligible EGFR mutation status as specified below: - EGFR TKI pre-treated patients: EGFRm+ (exon 19 deletions or L858R), along with valid T790M mutation status 5. --- L858R ---

3. Male and female patients must be at least 18 years of age. 4. Patients must have documented (only allowed for EGFRm+ [exon 19 deletions or L858R] in pre-treated patients) and/or confirmed central/local test result showing eligible EGFR mutation status as specified below: - EGFR TKI pre-treated patients: EGFRm+ (exon 19 deletions or L858R), along with valid T790M mutation status 5. --- L858R --- --- L858R ---

EGFR-TKIs are the standard first-line treatment option for EGFR-mutant NSCLC. After a randomized phase II trial, JO25567 was presented at 2014 ASCO, the synergistic effect of progression-free survival(PFS) could be expected when EGFR TKI, Gefitinib is combined with Antiangiogenesis agent thalidomide, Therefore Chinese data of treating EGFR mutation positive NSCLC patients with Gefitinib and thalidomide is significantly necessary for developing new standard treatment in first-line therapy in Chinese EGFR mutant NSCLC patients. In this study, The investigators will investigate the efficacy and safety of Gefitinib and thalidomide combination compare to Gefitinib alone in Chinese EGFR-mutant NSCLC patients.

NCT03341494

Conditions

1. NSCLC Stage IV
2. Chemotherapy Effect

Interventions

1. Drug: Thalidomide

Inclusion Criteria: - Pathologically confirmed stage IIIB & IV non-small cell lung cancer other than squamous cell carcinoma - Patients with one or more measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - Locally diagnosed sensitive EGFR mutation positive (Exon 19 deletion or L858R) - ECOG performance 0~1 - Age ≥ 19 years and - No previous treatment Adequate organ function by following: - ANC ≥1,500/uL, hemoglobin ≥9.0g/dL, platelet ≥100,000/uL - Serum bilirubin < 1 x UNL, AST (SGOT) and ALT (SGPT) < 2.5 x UNL, If Liver metastasis, Serum bilirubin < 3 x UNL, AST (SGOT) and ALT (SGPT) < 5 x UNL - Serum Cr ≤ 1 x UNL - Patients who have had undergone radiotherapy are acceptable if patients meet all of the following criteria: - No history of irradiation to pulmonary tumor lesions. --- L858R ---

- In case of irradiation to non-pulmonary sites: at least two weeks must have passed at the date of inclusion since the last irradiation of the sites - At the time of registration, at least the following period has passed since last date of the prior therapy or procedure: - Surgery(including exploratory/ examination thoracotomy): 4 weeks - Pleural cavity drainage: 1 weeks - Pleurodesis without anti-neoplastic agents (inclusive of BRM such as Picibanil): 2 week - Biopsy accompanied by incision (including thoracoscopic biopsy): 2 week - Procedure for trauma (exclusive of patients with unhealed wound): 2 weeks - Transfusion of blood, preparation of hematopoietic factor: 2 week - Puncture and aspiration cytology: 1 week - Other investigational product: 4 weeks - Written informed consent form Exclusion Criteria: - • Previous history of malignancy within 3 years from study entry except treated non-melanomatous skin cancer, uterine cervical cancer in situ, or thyroid cancer - Prior chemotherapy or systemic anti-cancer therapy for metastatic disease but postoperative adjuvant or neoadjuvant therapy of 6 months or more previously is allowed - Patients who received previous treatment for lung cancer with drugs - Symptomatic or uncontrolled central nervous system (CNS) metastases - Patients with increased risk of bleeding, clinically significant cardiovascular diseases, a history of thrombosis or thromboembolism in the 6 months prior to treatment, gastrointestinal problems, and neurologic problems - Any significant ophthalmologic abnormality - Pre-existing parenchymal lung disease such as pulmonary fibrosis - Known allergic history of Erlotinib or Bevacizumab - Interstitial lung disease or fibrosis on chest radiogram - Active infection, uncontrolled systemic disease (cardiopulmonary insufficiency, fatal arrhythmias, hepatitis) - Pregnant or nursing women Inclusion Criteria: - Pathologically confirmed stage IIIB & IV non-small cell lung cancer other than squamous cell carcinoma - Patients with one or more measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - Locally diagnosed sensitive EGFR mutation positive (Exon 19 deletion or L858R) - ECOG performance 0~1 - Age ≥ 19 years and - No previous treatment Adequate organ function by following: - ANC ≥1,500/uL, hemoglobin ≥9.0g/dL, platelet ≥100,000/uL - Serum bilirubin < 1 x UNL, AST (SGOT) and ALT (SGPT) < 2.5 x UNL, If Liver metastasis, Serum bilirubin < 3 x UNL, AST (SGOT) and ALT (SGPT) < 5 x UNL - Serum Cr ≤ 1 x UNL - Patients who have had undergone radiotherapy are acceptable if patients meet all of the following criteria: - No history of irradiation to pulmonary tumor lesions. --- L858R ---

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy given together with cisplatin is more effective with or without cetuximab in treating patients with cervical cancer. PURPOSE: This randomized phase II trial is studying giving radiation therapy together with cisplatin to see how well it works compared with radiation therapy and cisplatin given together with cetuximab in treating patients with stage IB, stage II, or stage IIIB cervical cancer.

NCT00957411

Conditions

1. Cervical Cancer

Interventions

1. Biological: cetuximab
2. Drug: cisplatin

MeSH:Uterine Cervical Neoplasms

HPO:Cervical polyp Cervix cancer

- Study the correlation between treatment response and analysis of EGFR mutations (exons 18-21 of the tyrosine kinase domain including the two hot spots L858R and E746-A750). --- L858R ---

In this research study erlotinib will be given to eligible participants whose lung cancer has been removed by surgery. Eligible patients have adenocarcinoma, a type of non-small lung cancer, and must have 1 or more of the following characteristics: be female, be of Asian or Pacific Rim descent and/or be a never smoker. The potential participant's tumor will be examined for Epidermal growth factor (EGFR) mutations. EGFR is a protein that is overexpressed in most non-small cell lung cancers. Some EGFR has been found to have specific mutations and the participant must have one of these mutations in his tumor. Erlotinib blocks this protein and may control tumor growth and increase survival. Previous research has shown that erlotinib is most effective for people who have these specific mutations in the EGFR.

NCT00567359

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Erlotinib

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

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

The median amount of time measured from the time of registration until the time of disease recurrence or death.. Inclusion Criteria: - Pathologically confirmed diagnosis of NSCLC of adenocarcinoma histology - Stage IA-B, IIA-B, or IIIA by the American Joint Committee on Cancer 7th edition staging criteria - Patients must have undergone surgical resection with curative intent within 6 months of enrollment - Sufficient tumor tissue available for EGFR mutation analysis - At least ONE of the following patient characteristics: previously detected deletion 19 or L858R EGFR mutation, female sex, history of never smoking, or Asian/Pacific Rim ethnicity (to be enrolled in the screening portion of trial). --- L858R ---

- 18 years of age or older - Tumor samples must have either exon 19 deletion mutations or the exon 21 L858R point mutation - ECOG Performance status of 0,1, or 2 - Adequate organ function as outlined in protocol Exclusion Criteria: - Radiographic evidence of recurrent NSCLC prior to erlotinib treatment - Confirmed T790M resistance mutation in the primary tumor sample - Prior exposure to EGFR tyrosine kinase inhibitors - Known hypersensitivity to erlotinib, gefitinib, or any closely related drug - Pregnant or breastfeeding women - Any evidence of clinically active interstitial lung disease - Current use of enzyme-inducing anti-epileptic drugs, including carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, and primidone - Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study - Use of any non-FDA approved or investigational agent within 2 weeks of enrolling onto the trial, or failure to recover from the side effects of any of these agents Inclusion Criteria: - Pathologically confirmed diagnosis of NSCLC of adenocarcinoma histology - Stage IA-B, IIA-B, or IIIA by the American Joint Committee on Cancer 7th edition staging criteria - Patients must have undergone surgical resection with curative intent within 6 months of enrollment - Sufficient tumor tissue available for EGFR mutation analysis - At least ONE of the following patient characteristics: previously detected deletion 19 or L858R EGFR mutation, female sex, history of never smoking, or Asian/Pacific Rim ethnicity (to be enrolled in the screening portion of trial). --- L858R ---

- 18 years of age or older - Tumor samples must have either exon 19 deletion mutations or the exon 21 L858R point mutation - ECOG Performance status of 0,1, or 2 - Adequate organ function as outlined in protocol Exclusion Criteria: - Radiographic evidence of recurrent NSCLC prior to erlotinib treatment - Confirmed T790M resistance mutation in the primary tumor sample - Prior exposure to EGFR tyrosine kinase inhibitors - Known hypersensitivity to erlotinib, gefitinib, or any closely related drug - Pregnant or breastfeeding women - Any evidence of clinically active interstitial lung disease - Current use of enzyme-inducing anti-epileptic drugs, including carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, and primidone - Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study - Use of any non-FDA approved or investigational agent within 2 weeks of enrolling onto the trial, or failure to recover from the side effects of any of these agents Inclusion Criteria: - Pathologically confirmed diagnosis of NSCLC of adenocarcinoma histology - Stage IA-B, IIA-B, or IIIA by the American Joint Committee on Cancer 7th edition staging criteria - Patients must have undergone surgical resection with curative intent within 6 months of enrollment - Sufficient tumor tissue available for EGFR mutation analysis - At least ONE of the following patient characteristics: previously detected deletion 19 or L858R EGFR mutation, female sex, history of never smoking, or Asian/Pacific Rim ethnicity (to be enrolled in the screening portion of trial). --- L858R --- --- T790M --- --- L858R ---

- 18 years of age or older - Tumor samples must have either exon 19 deletion mutations or the exon 21 L858R point mutation - ECOG Performance status of 0,1, or 2 - Adequate organ function as outlined in protocol Exclusion Criteria: - Radiographic evidence of recurrent NSCLC prior to erlotinib treatment - Confirmed T790M resistance mutation in the primary tumor sample - Prior exposure to EGFR tyrosine kinase inhibitors - Known hypersensitivity to erlotinib, gefitinib, or any closely related drug - Pregnant or breastfeeding women - Any evidence of clinically active interstitial lung disease - Current use of enzyme-inducing anti-epileptic drugs, including carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, and primidone - Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study - Use of any non-FDA approved or investigational agent within 2 weeks of enrolling onto the trial, or failure to recover from the side effects of any of these agents Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung - Erlotinib is a pill taken daily and participants may continue to receive erlotinib for up to two years, as long as the cancer does not return and they do not experience any unacceptable side effects. --- L858R ---

This phase II trial studies how well osimertinib with or without bevacizumab works in treating patients with EGFR positive non-small cell lung cancer that has spread to the brain (brain metastases). Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab may stop or slow non-small cell lung cancer by blocking the growth of new blood vessels necessary for tumor growth. Giving osimertinib with or without bevacizumab may work better in treating patients with non-small cell lung cancer.

NCT02971501

Conditions

1. Metastatic Lung Non-Small Cell Carcinoma
2. Metastatic Malignant Neoplasm in the Brain
3. Stage IV Lung Non-Small Cell Cancer AJCC v7

Interventions

1. Biological: Bevacizumab
2. Other: Laboratory Biomarker Analysis
3. Drug: Osimertinib

MeSH:Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm Non-small cell lung carcinoma

Analysis will be completed using Lasso-based elastic net method.. Inclusion Criteria: - Non-small cell lung cancer (NSCLC) with an activating EGFR mutation (exon 19 deletion, L858R point mutation, or any other mutation known to be associated with EGFR TKI sensitivity); presence of an activating EGFR mutation may be documented in tumor tissue or by plasma testing if performed in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory - No prior treatment with an EGFR TKI; patient may have received prior chemotherapy for early-stage or advanced disease but this is not required; prior immunotherapy is not allowed - Patients must have at least one measurable CNS lesion that is asymptomatic, untreated, and does not require local therapy at the time of enrollment; measurable CNS disease is defined as a brain metastasis that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 5 mm (>= 0.5 cm) with brain magnetic resonance imaging (MRI); if the lesion is 5-10 mm in size and is the only measurable disease, MRI imaging must be performed with 1.5 mm slice thickness or less; a history of previously treated brain metastases is allowed, however any lesion present at the time of whole brain radiotherapy or included in the stereotactic radiotherapy field (or within 2 mm of the treated lesion) will NOT be considered "untreated" unless it is new or documented to have progressed unequivocally since treatment - Patients are not required to have measurable systemic (i.e. --- L858R ---

aortic aneurysm, history of aortic dissection) - Clinically significant peripheral vascular disease - Any of the following cardiac criteria: - Mean resting corrected QT interval (Fridericia's correction formula [QTcF]) > 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived corrected QT (QTc) value - Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block) - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval - Evidence of bleeding diathesis or coagulopathy (including clinically significant hemoptysis) - Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9291 (osimertinib) - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies - Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior); all patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4 - Any evidence of severe or uncontrolled systemic diseases, including, but not limited to, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV); screening for chronic conditions is not required - History of hypersensitivity active or inactive excipients of AZD9291 (osimertinib) or drugs with a similar chemical structure or class to AZD9291 (osimertinib) - Absolute neutrophil count < 1.5 x 10^9/L - Platelet count < 100 x 10^9/L - Hemoglobin < 90 g/L - Alanine aminotransferase > 2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases; aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases - Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases - Serum creatinine > 1.5 times ULN concurrent with creatinine clearance < 50 mL/min (measured or calculated by Cockcroft and Gault equation)-confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN - 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: - Non-small cell lung cancer (NSCLC) with an activating EGFR mutation (exon 19 deletion, L858R point mutation, or any other mutation known to be associated with EGFR TKI sensitivity); presence of an activating EGFR mutation may be documented in tumor tissue or by plasma testing if performed in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory - No prior treatment with an EGFR TKI; patient may have received prior chemotherapy for early-stage or advanced disease but this is not required; prior immunotherapy is not allowed - Patients must have at least one measurable CNS lesion that is asymptomatic, untreated, and does not require local therapy at the time of enrollment; measurable CNS disease is defined as a brain metastasis that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 5 mm (>= 0.5 cm) with brain magnetic resonance imaging (MRI); if the lesion is 5-10 mm in size and is the only measurable disease, MRI imaging must be performed with 1.5 mm slice thickness or less; a history of previously treated brain metastases is allowed, however any lesion present at the time of whole brain radiotherapy or included in the stereotactic radiotherapy field (or within 2 mm of the treated lesion) will NOT be considered "untreated" unless it is new or documented to have progressed unequivocally since treatment - Patients are not required to have measurable systemic (i.e. --- L858R ---

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 ---

The purpose of this "first-in-human" study of PDR001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors. By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells. This study has been designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part. PDR001 will be administered every 2 weeks until patient experiences unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment is discontinued at the discretion of the investigator or the patient.

NCT02404441

Conditions

1. Melanoma
2. NSCLC
3. Triple Negative Breast Cancer
4. Anaplastic Thyroid Cancer
5. Other Solid Tumors

Interventions

1. Biological: PDR001

MeSH:Thyroid Neoplasms Triple Negative Breast Neoplasms Thyroid Carcinoma, Anaplastic

HPO:Anaplastic thyroid carcinoma Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). --- L858R ---

The purpose of this study is to determine the safety, tolerability, feasibility and preliminary efficacy of the administration of PBF-509 (Adenosine A2a receptor antagonist) as single agent or in combination with PDR001 (programmed cell death 1 receptor antibody (PD-1 Ab)) to NSCLC patients.

NCT02403193

Conditions

1. Non-small Cell Lung Cancer (NSCLC)

Interventions

1. Drug: PBF-509_80 mg
2. Drug: PBF-509_160 mg
3. Drug: PBF-509_320 mg
4. Drug: PBF-509_640 mg
5. Drug: Combo PBF-509 (160 mg) + PDR001
6. Drug: Combo PBF-509 (320 mg) + PDR001
7. Drug: Combo PBF-509 (640 mg) + PDR001
8. Drug: RP2D (PBF-509+PDR001)_immuno naïve
9. Drug: Experimental: RP2D (PBF-509+PDR001)_immuno treated

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

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

2. Patients must previously have received at least one prior line of therapy for their disease 3. EGFR mutation with exon 19 deletion or L858R mutation (Exon 21) or ALK rearrangement positive must have failed prior TKI therapy 4. Able, willing to give written consent for available archival tumor samples (not mandatory) and tumor biopsies before and during protocol therapy (mandatory). --- L858R ---

There is a medical need for improving treatment of poor performance status patients with EGFR driver mutations and documenting safety and tolerability of existing agents.

NCT02695290

Conditions

1. Carcinoma, Non-Small-Cell Lung
2. ErbB Receptors

Interventions

1. Drug: Afatinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

An Open-label, Single-arm Phase IV Study of Afatinib in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer Who Have Poor Performance Status and Whose Tumors Have the Common Epidermal Growth Factor Receptor (EGFR) Mutations, Exon 19 Deletions or Exon 21(L858R) Substitution Mutations. --- L858R ---

The staging is based on American Joint Committee on Cancer (AJCC) Tumor Node Metastatic (TNM) classification of malignant tumors, 7th edition - Evidence of common EGFR activating mutations (Del 19 and/or L858R) - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 or 3 - Adequate organ function, defined as all of the following: - Absolute neutrophil count (ANC) > 1500 / mm3 - Platelet count >75,000 / mm3. --- L858R ---

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 ---

The main purpose of this study is to evaluate the efficacy and safety of ramucirumab in combination with erlotinib as compared to placebo in combination with erlotinib in previously untreated participants with stage IV non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Exon 19-Del and Exon 21 L858R). Safety and tolerability of ramucirumab in combination with erlotinib will be assessed in Part A before proceeding to Part B. The purpose of Part C is to determine the efficacy and safety of ramucirumab in combination with gefitinib in previously untreated East Asian participants with EGFR mutation-positive metastatic NSCLC and of ramucirumab in combination with osimertinib in those participants whose disease progressed on ramucirumab and gefitinib and that have T790M - positive metastatic NSCLC.

NCT02411448

Conditions

1. Metastatic Non-Small Cell Lung Cancer

Interventions

1. Drug: Ramucirumab
2. Drug: Placebo
3. Drug: Erlotinib
4. Drug: Gefitinib
5. Drug: Osimertinib

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

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

A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY) The main purpose of this study is to evaluate the efficacy and safety of ramucirumab in combination with erlotinib as compared to placebo in combination with erlotinib in previously untreated participants with stage IV non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Exon 19-Del and Exon 21 L858R). --- L858R ---

- Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation [exon 19 deletion or exon 21 (L858R) substitution mutation]. --- L858R ---

Nicotinamide is an inhibitor of human sirtuins (HDAC III), and is found to re-activate epigenetically silenced tumor suppressors, RUNX3 (runt-related gene 3) and others, in cancer cells. Nicotinamide was found to be effective in several animal cancer models including lung, bladder, liver, etc. The purpose of this study is to determine whether nicotinamide is also effective in the treatment of human lung cancer.

NCT02416739

Conditions

1. Non-Small-Cell Lung Carcinoma

Interventions

1. Drug: Nicotinamide

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

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

Inclusion Criteria: - Operation-impossible stage 4 non-small-cell lung carcinoma (NSCLC), or recurred terminal stage NSCLC after previous operation or radiation therapy - EGFR mutated (exon 19 deletion or L858R mutation) - Life expectation more than 3 months - More than 1 measurable lesions by RECIST 1.1 which were not exposed to radiation previously - ECOG (Eastern Cooperative Oncology Group ) performance status grade 0~2 - Who signed the informed consent form Exclusion Criteria: - Who had received chemotherapy or EGFR tyrosin kinase inhibitors previously, except whom had received operation at least 6 months ago and received supplementary chemotherapy - Who has metastasized brain lesion that needs operation or radiation therapy - Above grade 2, CTCAE (Common Toxicity Criteria for Adverse Effects) 4.0 criteria for blood, liver and kidney - Who does Not agree to contraception - Who has allergy to nicotinamide Inclusion Criteria: - Operation-impossible stage 4 non-small-cell lung carcinoma (NSCLC), or recurred terminal stage NSCLC after previous operation or radiation therapy - EGFR mutated (exon 19 deletion or L858R mutation) - Life expectation more than 3 months - More than 1 measurable lesions by RECIST 1.1 which were not exposed to radiation previously - ECOG (Eastern Cooperative Oncology Group ) performance status grade 0~2 - Who signed the informed consent form Exclusion Criteria: - Who had received chemotherapy or EGFR tyrosin kinase inhibitors previously, except whom had received operation at least 6 months ago and received supplementary chemotherapy - Who has metastasized brain lesion that needs operation or radiation therapy - Above grade 2, CTCAE (Common Toxicity Criteria for Adverse Effects) 4.0 criteria for blood, liver and kidney - Who does Not agree to contraception - Who has allergy to nicotinamide Non-Small-Cell Lung Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung The standard therapy to the EGFR (epidermal growth factor receptor) mutation positive non-small-cell lung cancer patients who are not eligible to operation is to administer EGFR-TKIs (tyrosine kinase inhibitors, gefitinib or erlotinib). --- L858R ---

Inclusion Criteria: - Operation-impossible stage 4 non-small-cell lung carcinoma (NSCLC), or recurred terminal stage NSCLC after previous operation or radiation therapy - EGFR mutated (exon 19 deletion or L858R mutation) - Life expectation more than 3 months - More than 1 measurable lesions by RECIST 1.1 which were not exposed to radiation previously - ECOG (Eastern Cooperative Oncology Group ) performance status grade 0~2 - Who signed the informed consent form Exclusion Criteria: - Who had received chemotherapy or EGFR tyrosin kinase inhibitors previously, except whom had received operation at least 6 months ago and received supplementary chemotherapy - Who has metastasized brain lesion that needs operation or radiation therapy - Above grade 2, CTCAE (Common Toxicity Criteria for Adverse Effects) 4.0 criteria for blood, liver and kidney - Who does Not agree to contraception - Who has allergy to nicotinamide Inclusion Criteria: - Operation-impossible stage 4 non-small-cell lung carcinoma (NSCLC), or recurred terminal stage NSCLC after previous operation or radiation therapy - EGFR mutated (exon 19 deletion or L858R mutation) - Life expectation more than 3 months - More than 1 measurable lesions by RECIST 1.1 which were not exposed to radiation previously - ECOG (Eastern Cooperative Oncology Group ) performance status grade 0~2 - Who signed the informed consent form Exclusion Criteria: - Who had received chemotherapy or EGFR tyrosin kinase inhibitors previously, except whom had received operation at least 6 months ago and received supplementary chemotherapy - Who has metastasized brain lesion that needs operation or radiation therapy - Above grade 2, CTCAE (Common Toxicity Criteria for Adverse Effects) 4.0 criteria for blood, liver and kidney - Who does Not agree to contraception - Who has allergy to nicotinamide Non-Small-Cell Lung Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung The standard therapy to the EGFR (epidermal growth factor receptor) mutation positive non-small-cell lung cancer patients who are not eligible to operation is to administer EGFR-TKIs (tyrosine kinase inhibitors, gefitinib or erlotinib). --- L858R --- --- L858R ---

This study aims to evaluate the efficacy of icotinib, a first generation EGFR TKI, in non-small cell lung cancer patients harboring uncommon EGFR mutation

NCT02961270

Conditions

1. Non-small Cell Lung Cancer

Interventions

1. Drug: Icotinib

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

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

Inclusion Criteria: - Patients with stage IIIB/IV non-small cell lung cancer - Patients with uncommon epidermal growth factor receptor (EGFR) mutation - Targeted-therapy-naive patients - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 - Evaluable target lesions according to RECIST 1.1 for tumour response assessment Exclusion Criteria: - Wild-type EGFR - Positive 19 del and/or 21 L858R mutation - Previous treatment with EGFR TKIs such as gefitinib, erlotinib, and afatinib - Patients who have documented history of interstitial lung disease Inclusion Criteria: - Patients with stage IIIB/IV non-small cell lung cancer - Patients with uncommon epidermal growth factor receptor (EGFR) mutation - Targeted-therapy-naive patients - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 - Evaluable target lesions according to RECIST 1.1 for tumour response assessment Exclusion Criteria: - Wild-type EGFR - Positive 19 del and/or 21 L858R mutation - Previous treatment with EGFR TKIs such as gefitinib, erlotinib, and afatinib - Patients who have documented history of interstitial lung disease Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- L858R ---

Inclusion Criteria: - Patients with stage IIIB/IV non-small cell lung cancer - Patients with uncommon epidermal growth factor receptor (EGFR) mutation - Targeted-therapy-naive patients - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 - Evaluable target lesions according to RECIST 1.1 for tumour response assessment Exclusion Criteria: - Wild-type EGFR - Positive 19 del and/or 21 L858R mutation - Previous treatment with EGFR TKIs such as gefitinib, erlotinib, and afatinib - Patients who have documented history of interstitial lung disease Inclusion Criteria: - Patients with stage IIIB/IV non-small cell lung cancer - Patients with uncommon epidermal growth factor receptor (EGFR) mutation - Targeted-therapy-naive patients - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 - Evaluable target lesions according to RECIST 1.1 for tumour response assessment Exclusion Criteria: - Wild-type EGFR - Positive 19 del and/or 21 L858R mutation - Previous treatment with EGFR TKIs such as gefitinib, erlotinib, and afatinib - Patients who have documented history of interstitial lung disease Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- L858R --- --- L858R ---

The main purpose of this study is to evaluate the safety and efficacy of Apatinib in combination with Gefitinib as compared to placebo in combination with Gefitinib in participants with stage ⅢB-IV Non-squamous non-small-cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Del19 and L858R). Safety and tolerability of Apatinib in combination with Gefitinib will be assessed in the first portion (Part A) before proceeding to the second portion of this study (Part B).

NCT02824458

Conditions

1. EGFR Tyrosine Kinase Inhibitors Plus VEGFR Inhibitors

Interventions

1. Drug: Apatinib
2. Drug: Gefitinib
3. Drug: Placebo

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

A Study of Gefitinib With or Without Apatinib in Patients With Advanced Non-squamous Non-Small-Cell Lung Cancer Harboring EGFR Mutations The main purpose of this study is to evaluate the safety and efficacy of Apatinib in combination with Gefitinib as compared to placebo in combination with Gefitinib in participants with stage ⅢB-IV Non-squamous non-small-cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Del19 and L858R). --- L858R ---

5. Documented evidence of tumor harboring an activating EGFR mutation (Example 19 del and L858R) . --- L858R ---

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 ---

- 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 ---

The primary objective of this study is to determine if the combination regimen of ARQ 197 with erlotinib will improve overall survival (OS) compared to erlotinib monotherapy in subjects with locally advanced or metastatic non-squamous NSCLC with wild-type EGFR who have received 1 or 2 prior systemic anti-cancer therapies in the Intent-to-Treat (ITT) population.

NCT01377376

Conditions

1. Non-small-cell Lung Cancer

Interventions

1. Drug: ARQ 197 and Erlotinib
2. Drug: Placebo and Erlotinib

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

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

Inclusion Criteria 1. Male or female at least 20 years of age with life expectancy ≥ 3 months 2. Histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage IIIB/IV) non-squamous NSCLC with wild-type (excluding major activating mutation (exon 19 deletion and/or exon 21 L858R mutation)) EGFR gene status confirmed by a highly sensitive PCR assay 3. Evaluable disease according to RECIST, Version 1.1 4. Received one or two prior lines of systemic anti-cancer therapy for advanced or metastatic disease, one of which must be a platinum-based therapy 5. ECOG performance status of 0 or 1 6. --- L858R ---

Any other significant co-morbid condition that, in opinion of the investigator/sub-investigator, would impair study participation or cooperation Inclusion Criteria 1. Male or female at least 20 years of age with life expectancy ≥ 3 months 2. Histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage IIIB/IV) non-squamous NSCLC with wild-type (excluding major activating mutation (exon 19 deletion and/or exon 21 L858R mutation)) EGFR gene status confirmed by a highly sensitive PCR assay 3. Evaluable disease according to RECIST, Version 1.1 4. Received one or two prior lines of systemic anti-cancer therapy for advanced or metastatic disease, one of which must be a platinum-based therapy 5. ECOG performance status of 0 or 1 6. --- L858R ---

The purpose of this study is to determine whether Nivolumab, Ipilimumab combined with chemotherapy is more effective than chemotherapy by itself when treating stage IV NSCLC as the first treatment given for the disease

NCT03215706

Conditions

1. Non-Small Cell Lung Cancer

Interventions

1. Biological: Ipilimumab
2. Biological: Nivolumab
3. Drug: Carboplatin
4. Drug: Paclitaxel
5. Drug: Pemetrexed
6. Drug: Cisplatin

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

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

Inclusion Criteria: - Participants with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy - Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 - Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria - Participants must have PD-L1 IHC testing with results performed by a central laboratory during the screening period Exclusion Criteria: - Participants with known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded - Participants with known anaplastic lymphoma kinase (ALK) translocations which are sensitive to available targeted inhibitor therapy are excluded - Participants with untreated CNS metastases are excluded. --- L858R ---

This phase Ib trial studies the side effects and best dose of alisertib or sapanisertib, in combination with osimertinib, in treating patients with EGFR mutated stage IIIB or IV non-small cell lung cancer that remains despite treatment with osimertinib (osimertinib resistant). Osimertinib, alisertib, and sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The goal of part 1 of this trial is to find the highest tolerable dose of alisertib or sapanisertib in combination with osimertinib that can be given to patients with EGFR mutated non-small cell lung cancer. The goal of part 2 of this trial is to learn if the dose of alisertib or sapanisertib found in part 1 can help control EGFR mutated non-small cell lung cancer when given in combination with osimertinib.

NCT04479306

Conditions

1. EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma
2. Recurrent Lung Non-Small Cell Carcinoma
3. Stage IIIB Lung Cancer AJCC v8
4. Stage IV Lung Cancer AJCC v8
5. Stage IVA Lung Cancer AJCC v8
6. Stage IVB Lung Cancer AJCC v8

Interventions

1. Drug: Alisertib
2. Drug: Osimertinib
3. Drug: Sapanisertib

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

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

Estimated using the method of Kaplan and Meier.. Inclusion Criteria: - Patients must have histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - EGFR exon 21 L858R or exon 19 deletion mutation, or T790M mutation that was acquired following treatment with first or second generation tyrosine kinase inhibitor (TKI). --- L858R ---

- Female patient who intend to donate eggs (ova) during the course of this study or 180 days after receiving their last dose of study drug(s) - Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s) Inclusion Criteria: - Patients must have histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - EGFR exon 21 L858R or exon 19 deletion mutation, or T790M mutation that was acquired following treatment with first or second generation tyrosine kinase inhibitor (TKI). --- L858R ---

Lung cancer is the most common cancer in the world and the leading cause of cancer-related deaths in Western countries. Unfortunately, at the time of diagnosis, the majority of patients already have metastatic disease and a systemic, palliative treatment is the primary therapeutic option. Guidelines for PS 2 patients or older than 75 years old patients at the time of diagnosis recommend for fit patients a carboplatin doublet chemotherapy. Nivolumab has proven efficacy in 3rd line squamous cell lung carcinoma and is superior to chemotherapy in 2nd line treatment of squamous and non-squamous lung cancer in term of overall survival. In 1st line, nivolumab failed to show superiority compared to a platin based doublet in terms of progression free survival and overall survival in tumors ≥ 5% PD-L1 expression. The association Nivolumab plus Ipilimumab showed encouraging results in first line setting in phase 1 study. The investigators think that with regard to the manageable toxicity of nivolumab in lung cancer population and the possibility to obtain long responses, this association could be a valid option for this population of elderly and/or PS2 patients in term of overall survival.

NCT03351361

Conditions

1. Advanced Non Small Cell Lun
2. Advanced Non Small Cell Lung Cancer

Interventions

1. Drug: Nivolumab + Ipilimumab
2. Drug: Chemotherapy

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

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

- Known activating mutation of EGFR (del LREA exon 19, mutation L858R or L861X of exon 21, mutation G719A/S in exon 18) or EML4-ALK or ROS-1 translocation - Superior at caval syndrome - Uncontrolled infectious status - All concurrent radiotherapy - Concurrent administration of one or several other anti-tumor therapies. --- L858R ---

This is a multicenter, randomized, controlled, phase II study assessing the efficacy and safety of Almonertinib compared Erlotinib or platinum doublet chemotherapy (carboplatin or cisplatin + pemetrexed) as neoadjuvant therapy to EGFRm+ IIIA-N2 NSCLC patients.

NCT04455594

Conditions

1. Non-Small Cell Lung Cancer Stage IIIA

Interventions

1. Drug: Almonertinib
2. Drug: Erlotinib
3. Drug: Cisplatin
4. Drug: Carboplatin
5. Drug: Pemetrexed

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

3. Tumor tissue samples or blood samples are confirmed as EGFR sensitive mutations by central laboratory tests (including Ex19del or L858R, both alone or with other EGFR mutations). --- L858R ---

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 ---

A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib.

NCT03239340

Conditions

1. EGFR Mutation Positive Locally Advanced or Metastatic 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

PFS will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, epidermal growth factor receptor (EGFR) Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived circulating tumour deoxyribonucleic acid (ctDNA).. ORR in patient subgroups defined by molecular profile. --- T790M --- --- L858R ---

PFS will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, epidermal growth factor receptor (EGFR) Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived circulating tumour deoxyribonucleic acid (ctDNA).. ORR in patient subgroups defined by molecular profile. --- T790M --- --- L858R --- --- L858R ---

ORR will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.. TTD in patient subgroups defined by molecular profile. --- T790M --- --- L858R ---

ORR will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.. TTD in patient subgroups defined by molecular profile. --- T790M --- --- L858R --- --- L858R ---

TTD will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.. Tumour shrinkage/depth of response in patient subgroups defined by molecular profile. --- T790M --- --- L858R ---

TTD will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.. Tumour shrinkage/depth of response in patient subgroups defined by molecular profile. --- T790M --- --- L858R --- --- L858R ---

Tumour shrinkage/depth of response will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.. Proportion of patients with pre-specified characteristics will be summarised by molecular profile. --- T790M --- --- L858R ---

Tumour shrinkage/depth of response will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.. Proportion of patients with pre-specified characteristics will be summarised by molecular profile. --- T790M --- --- L858R --- --- L858R ---

These will be summarized by subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.. Adverse events graded by Common Terminology Criteria for Adverse Events version 4.0. --- T790M --- --- L858R ---

These will be summarized by subgroups defined by molecular profile, including but not limited to: Positive pre-treatment T790M mutation, EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA.. Adverse events graded by Common Terminology Criteria for Adverse Events version 4.0. --- T790M --- --- L858R --- --- L858R ---

This is a non-interventional, multi-country, multi-centre cohort study based on existing data from medical records of patients with EGFR mutation-positive advanced NSCLC treated with afatinib (Gi(l)otrif®) as the first-line treatment followed by osimertinib in case the T790M resistance mutation was developed.

NCT03370770

Conditions

1. Carcinoma, Non-Small-Cell Lung

Interventions

1. Drug: Afatinib
2. Drug: Osimertinib

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

HPO:Non-small cell lung carcinoma

Different types of resistance mutations identified at the time of discontinuation of osimertinib treatment were systematically reviewed and categorised.. Inclusion Criteria: - Patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) - The tumour harbours common EGFR mutations (Del19, L858R) at start of first-line treatment - Patients who initiated second-line osimertinib treatment for acquired T790M mutation at least 10 months prior to data entry, AND who were treated with afatinib (Gi(l)otrif®) in the first-line - Patients treated with osimertinib within an EAP/CUP or regular clinical practice - Age ≥ 18 years - Signed and dated written informed consent per regulations (Exemption of a written informed consent for NIS based on existing data in countries per local regulations and legal requirements) Exclusion Criteria: - Patients who received drug(s) other than osimertinib as the second-line treatment and/or patients who received drug(s) other than afatinib (Gi(l)otrif®) as the first-line treatment - Patients with active brain metastases at start of treatment (either afatinib/Gi(l)otrif® or osimertinib) Inclusion Criteria: - Patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) - The tumour harbours common EGFR mutations (Del19, L858R) at start of first-line treatment - Patients who initiated second-line osimertinib treatment for acquired T790M mutation at least 10 months prior to data entry, AND who were treated with afatinib (Gi(l)otrif®) in the first-line - Patients treated with osimertinib within an EAP/CUP or regular clinical practice - Age ≥ 18 years - Signed and dated written informed consent per regulations (Exemption of a written informed consent for NIS based on existing data in countries per local regulations and legal requirements) Exclusion Criteria: - Patients who received drug(s) other than osimertinib as the second-line treatment and/or patients who received drug(s) other than afatinib (Gi(l)otrif®) as the first-line treatment - Patients with active brain metastases at start of treatment (either afatinib/Gi(l)otrif® or osimertinib) Carcinoma, Non-Small-Cell Lung Carcinoma, Non-S Carcinoma, Non-Small-Cell Lung null --- L858R ---

Different types of resistance mutations identified at the time of discontinuation of osimertinib treatment were systematically reviewed and categorised.. Inclusion Criteria: - Patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) - The tumour harbours common EGFR mutations (Del19, L858R) at start of first-line treatment - Patients who initiated second-line osimertinib treatment for acquired T790M mutation at least 10 months prior to data entry, AND who were treated with afatinib (Gi(l)otrif®) in the first-line - Patients treated with osimertinib within an EAP/CUP or regular clinical practice - Age ≥ 18 years - Signed and dated written informed consent per regulations (Exemption of a written informed consent for NIS based on existing data in countries per local regulations and legal requirements) Exclusion Criteria: - Patients who received drug(s) other than osimertinib as the second-line treatment and/or patients who received drug(s) other than afatinib (Gi(l)otrif®) as the first-line treatment - Patients with active brain metastases at start of treatment (either afatinib/Gi(l)otrif® or osimertinib) Inclusion Criteria: - Patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) - The tumour harbours common EGFR mutations (Del19, L858R) at start of first-line treatment - Patients who initiated second-line osimertinib treatment for acquired T790M mutation at least 10 months prior to data entry, AND who were treated with afatinib (Gi(l)otrif®) in the first-line - Patients treated with osimertinib within an EAP/CUP or regular clinical practice - Age ≥ 18 years - Signed and dated written informed consent per regulations (Exemption of a written informed consent for NIS based on existing data in countries per local regulations and legal requirements) Exclusion Criteria: - Patients who received drug(s) other than osimertinib as the second-line treatment and/or patients who received drug(s) other than afatinib (Gi(l)otrif®) as the first-line treatment - Patients with active brain metastases at start of treatment (either afatinib/Gi(l)otrif® or osimertinib) Carcinoma, Non-Small-Cell Lung Carcinoma, Non-S Carcinoma, Non-Small-Cell Lung null --- L858R --- --- T790M --- --- L858R ---

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 ---

This is a Phase 4, open label, single arm, multi-center, prospective clinical trial of dacomitinib that will be performed in India. This study will enroll a sufficient number of participants to ensure that 100 participants are treated with dacomitinib. The primary objective of this study is to assess the safety and tolerability of dacomitinib. The secondary objective is to evaluate antitumor activity of dacomitinib by objective response rate and duration of response.

NCT04511533

Conditions

1. Metastatic 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

2. Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation. --- L858R ---

The purpose of this study is to develop a real-time diagnostic technique with e- Ab sensor for specific EGFR mutation detection in clinical specimens of NSCLC patients, the investigators conduct a prospective clinical study. In comparison with results from direct sequencing of EGFR, the investigators evaluate the performance of e- Ab sensor, including reproducibility, sensitivity, specificity, and cross-reaction (such as detection of EGFR mutations other than L858R and DelL746-A750). The potential factors which may interfere with the results would be investigated. With such technique, the investigators can obtain EGFR mutation information of NSCLC patients in cost-saving and time-saving way and can offer more individualized treatment for the investigators patients.

NCT01359436

Conditions

1. Non-small Cell Lung Cancer (NSCLC)

Interventions

1. Device: Electrosensing antibody probing system (e- Ab sensing)

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

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

In comparison with results from direct sequencing of EGFR, the investigators evaluate the performance of e- Ab sensor, including reproducibility, sensitivity, specificity, and cross-reaction (such as detection of EGFR mutations other than L858R and DelL746-A750). --- L858R ---

In comparison with results from direct sequencing of EGFR, we evaluate the performance of e- Ab sensor, including reproducibility, sensitivity, specificity, and cross-reaction (such as detection of EGFR mutations other than L858R and DelL746-A750). --- L858R ---

However, only some EGFR mutations are associated with sensitivity to tyrosine kinase inhibitor treatment, especially deletion in exon 19 and L858R mutation in exon 21.4-5 Two recent phase III randomized clinical trials evaluated gefitinib treatment and chemotherapy in patients of advanced NSCLC with sensitive EGFR mutaions.6-7 --- L858R ---

8 For detection for specific EGFR mutations, mutation-specific monoclonal antibodies were developed to detect E746-A750 deletion in exon 19 and L858R in exon 21. --- L858R ---

In the study by Akhiko Kawahara et al, IHC assay of NSCLC tumor specimens with anti-delE746-A750 antibody showed a sensitivity of 79%, which was 83% by IHC assay with anti-L858R antibody.10 --- L858R ---

IHC assay with anti-L858R antibody also showed high specificity but low sensitivity (97% and 36%, respectively). --- L858R ---

For anti-L858R antibody, the sensitivity was 76%-95% and the positive predicted value was 99%-100%. --- L858R ---

Electrosensing antibody probing system (e- Ab sensor), which was developed for the rapid and sensitive detection of hapten, proteins, or viral antigen in medical samples, will be used for analyzing the interaction kinetics between mutation specific anti-EGFR and its antigen (EGFR with E746-A750 deletion or L858R mutation) present in the specimens of patients with lung cancer. --- L858R ---

In comparison with results from direct sequencing of EGFR, we evaluate the performance of e- Ab sensor, including reproducibility, sensitivity, specificity, and cross-reaction (such as detection of EGFR mutations other than L858R and DelL746-A750). --- L858R ---

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 ---

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 ---

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 ---

- 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 ---

This randomized phase II/III trial studies how well afatinib dimaleate with cetuximab works and compares it with afatinib dimaleate alone in treating patients with newly diagnosed stage IV or recurrent (has come back), epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer. Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether afatinib dimaleate is more effective when given alone or with cetuximab in treating patients with non-small cell lung cancer.

NCT02438722

Conditions

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

Interventions

1. Drug: Afatinib Dimaleate
2. Biological: Cetuximab
3. Other: Laboratory Biomarker Analysis

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

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