SNPMiner Trials by Shray Alag


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Report for Mutation C797S

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 13 clinical trials

Clinical Trials


1 A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer

The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of JNJ-61186372 as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose (RP2q3W) with combination chemotherapy (JNJ-61186372 in combination with standard of care carboplatin and pemetrexed) in 21 day treatment cycle for participants with advanced non-small cell lung cancer (NSCLC).

NCT02609776 Non-Small-Cell Lung Cancer Drug: JNJ-61186372 Drug: JNJ-61186372 Drug: Lazertinib Drug: Carboplatin Drug: Pemetrexed
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

Cohort C: Participants with primary EGFR mutated disease, with a documented EGFR alteration (example, C797S) mediating resistance to previous treatment with a third generation EGFR TKI (for example, osimertinib), in participants with primary Exon 20ins disease, the documented EGFR alteration may arise following treatment with a TKI with known activity against Exon 20ins disease (for example, poziotinib). --- C797S ---

Primary Outcomes

Description: The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury.

Measure: Part 1: Number of Participants With Dose Limiting Toxicity (DLT)

Time: Up to Day 28

Description: An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Measure: Part 2: Number of Participants With Adverse Events (AEs) and Serious AEs

Time: Screening up to follow-up (30 [+7] days after the last dose)

Description: Overall response rate (ORR) is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). CR: disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (< 10 mm short axis) and normalisation of tumour marker levels; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

Measure: Part 2: Overall Response Rate (ORR)

Time: Up to End of Treatment Follow (EOT) Up Period (30 [+7] days after the last dose)

Description: DOR will be calculated as time from initial response of CR (disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size ([<] 10 [mm] short axis) and normalisation of tumour marker levels) or PR (at least a 30 [%] decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits) to progressive disease (PD) or death due to underlying disease, whichever comes first, only for participants who achieve CR or PR.

Measure: Part 2: Duration of Response (DOR)

Time: Up to EOT Follow Up Period (30 [+7] days after the last dose)

Description: Clinical benefit rate is defined as the percentage of participants achieving complete response (CR): disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (less than [<] 10 millimeter [mm] short axis) and normalisation of tumour marker levels or partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

Measure: Part 2: Percentage of Participants With Clinical Benefit

Time: Up to EOT Follow Up Period (30 [+7] days after the last dose)

Description: Ctrough is the observed serum concentration immediately prior to the next administration.

Measure: Trough Serum Concentration (Ctrough) of JNJ-61186372

Time: Up to EOT (30 days after last dose)

Description: The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

Measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-61186372

Time: Up to EOT (30 days after last dose)

Secondary Outcomes

Description: The Cmax is the maximum observed serum concentration of JNJ-61186372.

Measure: Maximum Serum Concentration (Cmax) of JNJ-61186372

Time: Cycle 1 Day 1: predose through end of infusion (EOT) or Follow Up (approximately 16 months) (each cycle is of 28 days)

Description: The Tmax is defined as time to reach maximum observed serum concentration of JNJ-61186372.

Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The AUC(t1-t2) is the area under the serum JNJ-61186372 concentration-time curve from time t1 to t2.

Measure: Area Under the Serum Concentration-Time Curve From t1 to t2 Time (AUC[t1-t2]) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

Measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The Ctrough is the observed serum concentration immediately prior to the next administration.

Measure: Trough Serum Concentration (Ctrough) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: Cmax is the maximum observed serum concentration of lazertinib.

Measure: Maximum Serum Concentration (Cmax) of Lzertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: Tmax is defined as time to reach maximum observed serum concentration of lazertinib.

Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of Lazertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: Ctrough is the observed serum concentration immediately prior to the next administration.

Measure: Trough Serum Concentration (Ctrough) of Lazertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: The R is the accumulation ratio calculated as Cmax or AUC after multiple doses divided by Cmax or AUC after the first dose, respectively.

Measure: Accumulation ratio (R) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: Serum levels of antibodies to JNJ-61186372 for evaluation of potential immunogenicity.

Measure: Number of Participants With Anti-Drug Antibodies (ADA)

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: PFS is defined as the time from first infusion of study drug to PD or death due to any cause.

Measure: Progression-Free Survival (PFS)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Description: TTF is defined as the time from the first infusion of the study drug to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond RECIST v1.1 defined disease progression.

Measure: Time to Treatment Failure (TTF)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Description: OS is defined as the time from first infusion of study drug to death due to any cause.

Measure: Overall Survival (OS)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

2 A Pilot Study of Local Ablative Therapy for Treatment of Oligoprogressive, EGFR-mutated, Non-Small Cell Lung Cancer (NSCLC) After Treatment With Osimertinib (AZD9291, Tagrisso)

Background: Some non-small-cell lung cancers (NSCLC) have a mutation in a gene that makes a protein called EGFR. This particular cancer can be treated with certain drugs such as Erlotinib (Tarceva), Gefitinib (Iressa) and Osimertinib (Tagrisso). But many tumors become resistant to these drugs because of a second mutation. Researchers want to test if adding local ablative therapy (LAT) extends the benefits of the drug, Osimertinib. LAT can include techniques such as surgery, radiofrequency ablation, cryotherapy or radiation therapy. Objective: To test if re-taking osimertinib after LAT is safe, tolerable, and effective for people whose NSCLC has progressed after initial treatment with osimertinib. Eligibility: Adults ages 18 and older with certain types of NSCLC. Participants will be divided into various groups as described below. Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Tumor scans Eye exam Review of tumor sample. Participants will take the study drug by mouth once a day. They will continue until they can no longer tolerate it or their disease worsens. They will keep a dosage diary. All participants will start each 21-day course with physical exam; blood, urine, and saliva tests; and electrocardiogram. They will have scans every 6 weeks and echocardiogram every 3 months. Groups 1 and 2 will: Start osimertinib right away. Have LAT if their disease gets worse and is suitable for LAT. If LAT cannot be performed or LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Re-start osimertinib after LAT, or other treatments if not suitable for LAT. Group 3 will: Have LAT. If LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Start osimertinib after LAT. After participants stop taking the drugs, they will have a final visit. This will include: Medical history Physical exam Heart and blood tests Participants will be called every year for follow-up.

NCT02759835 Lung Adenocarcinoma Lung Neoplasms Drug: osimertinib Other: LAT
MeSH:Lung Neoplasms Adenocarcinoma of Lung
HPO:Neoplasm of the lung

In fact, a newly identified EGFR mutation (C797S) that results in acquired resistance to osimertinib has been reported recently. --- C797S ---

Primary Outcomes

Description: progression-free survival (PFS)

Measure: determine PFS in patients with oligoprogressive disease after treatment with LAT followed by osimertinib

Time: progression of disease

Description: time to second progression (PFS2)

Measure: Patients who progress on their initial treatment with osimertinib and receive LAT therapy (surgery, radiation therapy, or RFA) followed by osimertinib will be evaluated for their time to second progression (PFS2)

Time: progression of disease

Secondary Outcomes

Description: response rate

Measure: response rate

Time: end of treatment

Description: overall survival

Measure: overall survival

Time: death

Description: EGFR mutation status using liquid biopsies

Measure: feasibility of evaluating EGFR mutation status using liquid biopsies

Time: end of treatment

3 A Longitudinal Study Evaluating Molecular Changes Associated With Resistance to First and Third (AZD9291) Generation EGFR TKIs in Patients With EGFR Mutant NSCLC Using "Liquid Biopsy"

Based on the possibilities that both plasma and circulating tumor cells (CTCs) (the "liquid biopsy") may offer, we consider that it could be feasible to longitudinally monitor the genetic evolution and the biologic characteristics of CTCs, by using Circulating tumor DNA (ctDNA) and CTCs as a source of biologic material. This approach could provide information regarding the genetic/molecular changes associated with primary and acquired resistance to AZD9291 and, thus, to facilitate to more appropriately adapt the tailored treatment in this particular group of NSCLC patients. It has been recently reported that the detection of resistant clones, based on the tumor-associated genetic aberrations in the blood, can identify treatment resistance up to 10 months earlier than the radiological methods providing, thus, the potential for an early switch to a non cross-resistant therapy in order to improve patients' outcome.

NCT02771314 Non Small Cell Lung Cancer Drug: AZD9291
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

The patients will be followed every 3 months for the detection of mutations (T790M), (C797S), (L858R), del 19 EGFR mutations as well as the mutations [(KRAS)/(NRAS), (BRAF), (PI3K)] in the serum/plasma, the determination of the serum levels of Hepatocyte Growth Factor (HGF), the presence of T790M (+) and C797S(+) CTCs as well as the molecular (c-MET) and (HER2 amplification) and phenotypic characterization of CTCs using the filtration platform (ISET). --- T790M --- --- C797S ---

Primary Outcomes

Measure: Biomarkers of resistance to first and third (AZD9291) generation EGFR TKIs, explored by studying baseline serial serum or plasma DNA specimens and baseline Circulating Tumor Cells (CTCs)

Time: Up to 2.5 years

Secondary Outcomes

Measure: Progression free survival (PFS)

Time: Up to 2.5 years

Measure: Overall Survival

Time: Up to 2.5 years

Measure: Response rate, assessed using RECIST 1.1

Time: Up to 2.5 years

4 Clinical Study of Yiqi-yangyin-jiedu Decoction Combined With Gefitinib in Advanced Pulmonary Adenocarcinoma Patients With Activating EGFR Mutation

The investigators performed a multi-centered, randomized, double blinded, placebo-controlled, prospective clinical trial on the effect of Yiqi-yangyin-jiedu decoction (YYJD), a chinese herbal medicine (CHM) formula combined with gefitinib to prolong the progression free survival (PFS) of advanced pulmonary adenocarcinoma patients with activating EGFR mutation (exon19del or exon21L858R). The investigators plan to enroll 198 cases in 3 years (99 cases for gefitinib, 99 cases for gefitinib plus YYJD), expecting that combination therapy has a better efficacy on prolonging PFS, overall survival, improving quality of life(QOL).

NCT02929693 Cancer Drug: gefitinib Drug: Yiqi-yangyin-jiedu decoction Drug: placebo
MeSH:Adenocarcinoma Adenocarcinoma of Lung

Although AZD9291 (AstraZeneca), a third-generation EGFR-TKI is reported with a response rate of 61% in NSCLC patients with EGFR T790M and a mPFS of 9.6 months, resistance to third-generation inhibitors mediated by EGFR C797S mutation is inevitable. --- T790M --- --- C797S ---

Primary Outcomes

Description: Time from start of the study treatment to date of objective tumour progression (excluding clinical deterioration without evidence of objective progression).

Measure: Progression-free survival (PFS)

Time: 2 months

Secondary Outcomes

Description: interval time from the first date of randomization to that of death for any reason, the end of the study, or loss of follow-up

Measure: Overall survival (OS)

Time: 2 months

Description: The ORR (complete response (CR) plus partial response (PR)) was determined by the Response Evaluation Criteria In Solid Tumors (RECIST) (Eisenhauer et al, 2009) version 1.1.in Solid Tumors (RECIST1.1).

Measure: Objective response rate (ORR)

Time: 2 months

Description: QOL is assessed using Functional Assessment of Cancer therapy-lung (FACT-L) questionnaire .

Measure: Quality of life (QOL)

Time: 2 months

Description: Safety assessment is evaluated according to Common Toxicity Criteria (CTC 3.0).

Measure: Safety assessment evaluated according to Common Toxicity Criteria

Time: 2 months

5 A Study of T790M Mutation Testing in Patient Tissue and Blood With Various Detection Platforms at Hospital Laboratories in Comparison With Central Testing

The study primary objective is to assess the concordance of T790M resistance mutation testing from hospital-based laboratories with T790M resistance mutation testing from a central laboratory.

NCT02991274 Locally Advanced or Me Locally Advanced or Metastatic EGFR(+) NSCLC Patients Procedure: genomic testing of T790M mutation

The prevalence of C797S (An amino acid substitution at position 797 in EGFR, from a Cysteine (C) to a Serine (S) ) resistance mutation based on the local lab testing. --- C797S ---

Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%. --- C797S ---

Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%. --- C797S --- --- C797S ---

Primary Outcomes

Description: Concordance (%)=(number of patients with same T790M mutation status based on central and local labs)/(total number of patients in the FAS) ×100%

Measure: the concordance of T790M mutation testing between the test in central and local labs

Time: within 1 -14 days after enrolled

Secondary Outcomes

Description: Prevalence (%) = (number of patients with T790M mutation positive)/(total number of patients in the FAS)×100%

Measure: The prevalence rate of T790M mutation based on the central lab testing

Time: within 1 -14 days after enrolled

Description: Sensitivity (%)=(number of patients with T790M mutation positive based on both tissue and plasma tests)/(number of patients with T790M mutation positive based on tissue test) ×100%

Measure: The sensitivity of each platform based on the local lab plasma testing

Time: within 1 -14 days after enrolled

Description: Specificity (%)=(number of patients with T790M mutation negative based on both tissue and plasma tests)/(number of patients with T790M mutation negative based on tissue test) ×100%

Measure: The Specificity of each platform based on the local lab plasma testing

Time: within 1 -14 days after enrolled

Description: Positive predictive value (%)=(number of patients with T790M mutation positive based on both tissue and plasma tests)/(number of patients with T790M mutation positive based on plasma test) ×100%

Measure: The Positive predictive value of each platform based on the local lab plasma testing

Time: within 1 -14 days after enrolled

Description: Negative predictive value (%)=(number of patients with T790M mutation negative based on both tissue and plasma tests)/(number of patients with T790M mutation negative based on plasma test) ×100%

Measure: The Negative predictive value of each platform based on the local lab plasma testing

Time: within 1 -14 days after enrolled

Description: Concordance (%)=(number of patients with same T790M mutation status based on tissue and plasma tests)/(total number of patients in the FAS) ×100%

Measure: The Concordance of each platform based on the local lab testing

Time: within 1 -14 days after enrolled

Description: Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%

Measure: The prevalence of C797S (An amino acid substitution at position 797 in EGFR, from a Cysteine (C) to a Serine (S) ) resistance mutation based on the local lab testing

Time: within 1 -14 days after enrolled

Description: Prevalence (%) = (number of patients with rare EGFR mutation positive)/(total number of patients in the FAS)×100%

Measure: Rare EGFR mutation prevalence rate

Time: within 1-14 days after enrolled

6 Detect EGFR T790M Mutation in ctDNA of Chinese Advanced/Metastatic NSCLC Patients by Cobas, Super-ARMS, Digital PCR and NGS and Evaluate Clinical Outcomes of T790M Mutation Positive Patients Who Had AZD9291 Monotherapy

The aim of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

NCT02997501 Lung Cancer Procedure: T790M+ Testing Procedure: Baseline Visit Blood & Urine Testing Procedure: Baseline ECG Procedure: Visual Slit-Lamp Testing Drug: AZD9291 Dosing Procedure: Plasma AZD9291 testing

To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.. Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.. --- C797S ---

Primary Outcomes

Description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and Super-ARMS platform.

Measure: Concordance of T790M mutation plasma testing between Cobas test and Super-ARMS platform

Time: Within 1- 28 days after enrollment and before study treatment

Description: To assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR- TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

Measure: Progression Free Survival (PFS) using investigator assessments according to RECIST v1.1

Time: From first dose intake to Progression of disease (PD), up to 3 years

Description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and digital PCR platform.

Measure: Concordance of T790M mutation plasma testing between Cobas test and digital PCR platform

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and NGS platform.

Measure: Concordance of T790M mutation plasma testing between Cobas test and NGS platform

Time: Within 1- 28 days after enrollment and before study treatment

Secondary Outcomes

Description: To evaluate the sensitivity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Measure: Testing sensitivity

Time: Within 1- 28 days after enrollment and before study treatment

Description: To assess the efficacy of AZD9291 monotherapy by assessment of ORR in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

Measure: Objective Response Rate (ORR)

Time: From first dose intake to end of study, up to 3 years

Description: To assess the efficacy of AZD9291 monotherapy by assessment of OS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

Measure: Overall Survival (OS)

Time: From first dose intake to end of study, up to 3 years

Description: To evaluate the specificity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Measure: Testing specificity

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate PPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Measure: Testing positive predictive value (PPV)

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Measure: Testing negative predictive value (NPV)

Time: Within 1- 28 days after enrollment and before study treatment

Other Outcomes

Description: To dynamically monitor EGFR mutations by NGS and digital PCR in ctDNA of patients receiving AZD9291 treatment.

Measure: Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.

Time: every 6 weeks during treatment, up to 3 years

Description: To explore the mechanisms of acquired resistance in patients who received AZD9291 treatment by NGS testing of tissue and/or blood samples from the collection at PD versus baseline.

Measure: Changes of distribution of resistance related genes at PD compared with baseline.

Time: every 6 weeks during treatment, up to 3 years

Description: To describe the genomic profile of long-term survivors, especially to find out potential genomic prognosis and/or predictive factors for AZD9291 long-term efficacy as compared to rapid PD patients.

Measure: Key genetic and proteomic markers including, but not limited to, EGFR mutations

Time: every 6 weeks during treatment, up to 3 years

Description: To evaluate concordance of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing concordance

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate sensitivity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing sensitivity

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate specificity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing specificity

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate PPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing positive predictive value (PPV)

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate NPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing negative predictive value (NPV)

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.

Measure: Objective Response Rate (ORR)

Time: From first dose intake to end of study, up to 3 years

Description: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.

Measure: Progression Free Survival (PFS)

Time: From first dose intake to end of study, up to 3 years

Description: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.

Measure: Overall Survival (OS)

Time: From first dose intake to end of study, up to 3 years

7 Prospective Observational Trial to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Disease Progression to 3st Generation Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor(EGFR-TKI) Osimertinib

The third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor(EGFR-TKI) osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

NCT03532698 Non-Small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV EGFR T790M Drug: Aspirin Drug: Osimertinib
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---

Primary Outcomes

Description: To evaluate the response to therapy and Objective Response Rate of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.

Measure: Objective Response Rate(ORR) according to resist 1.1

Time: 2years

Secondary Outcomes

Description: To evaluate the response to therapy and disease control rate of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.

Measure: disease control rate(DCR) according to resist 1.1

Time: 2years

Description: To evaluate the response to therapy and Time to progression of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.

Measure: Time to progression(TTP) according to resist 1.1

Time: 2years

Description: To evaluate the response to therapy and duration of Response of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.

Measure: duration of Response(DOR) according to resist 1.1

Time: 2years

8 Prospective Observational Trial to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Disease Progression to 1st Generation EGFR-TKI Due to Acquisition of EGFR T790M

The third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor(EGFR-TKI) osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

NCT03543683 Non-Small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV EGFR T790M Drug: Osimertinib Drug: Aspirin
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---

Primary Outcomes

Description: To evaluate the response to therapy and 1 year median progression-free survival(PFS) rates of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .

Measure: 1-year median progression-free survival(PFS) rates according to resist 1.1

Time: 3years

Secondary Outcomes

Description: To evaluate the response to therapy and 1 year progression-free survival (PFS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .

Measure: median PFS according to resist 1.1

Time: 3years

Description: To evaluate the response to therapy and overall survival(OS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI

Measure: median overall survival(OS) according to resist 1.1

Time: 3years

9 Whole Genomic Landscape of EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Treated With First-Line Osimertinib (WARRIOR)

This is a phase 2 single-arm, non-randomized multicentre and tissue acquisition study to evaluate acquired resistance mechanisms, efficacy, and safety in advanced, EGFR tyrosine kinase inhibitor-naïve NSCLC patients with EGFR-activating mutations who receive a first-line osimertinib orally at a dose of 80mg once daily.

NCT03969823 Locally Advanced or Metastatic NSCLC Drug: Tagrisso
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

Acquired resistance to first-line osimertinib is mediated by heterogeneous mechanisms including MET amplification (15%), secondary EGFR mutation including C797S or S768I (7%), PIK3CA mutation (7%), CDK4/6 amplification (5%), KRAS mutation (3%), BRAF mutation (3%), CCND1-3 amplification (3%), CCNE1 amplification (2%), HER2 amplification (2%), and SPTBN1-ALK fusion (1%) using plasma genotyping of FLAURA study (N=91). --- C797S ---

Primary Outcomes

Description: Disease progression as defined by investigator assessments according to RECIST1.1

Measure: Proportion of acquired resistance mechanisms to osimertinib at disease progression

Time: Through study completion, an average of 2 years

Secondary Outcomes

Description: AEs/SAEs as defined by NCI CTCAE version 5.0

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: Through study completion, an average of 2 years

Description: PFS as defined as the time from the date of initiation until the date of first documented progression

Measure: Progression-Free Survival (PFS)

Time: Through study completion, an average of 2 years

Description: OS as defined as the time from the date of first dose until death due to any cause

Measure: Overall Survival (OS)

Time: Through study completion, an average of 2 years

Description: ORR using investigator assessments according RECIST1.1

Measure: Objective Response Rate (ORR)

Time: Through study completion, an average of 2 years

10 A Multi-center, One-arm, Phase II Trial of Anlotinib Combined With Osimertinib as the Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M.

Evaluate the efficacy and safety of Anlotinib combined with Icotinib as the second-line treatment in stage IIIb-IV NSCLC patients with sensitive EGFR and T790M mutations.

NCT04029350 Non Small Cell Lung Cancer Drug: Anlotinib Combined With Osimertinib
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

Exclusion Criteria: 1. Squamous cell carcinoma (including adenosquamous carcinoma); Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer) 2. Non-small cell lung cancer (NSCLC) with an EGFR C797S mutation. --- C797S ---

Primary Outcomes

Description: The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"

Measure: Progression-free survival (PFS)

Time: each 42 days up to PD or death (up to 24 months)

Secondary Outcomes

Description: OS was defined as time from date of enrollment to date of death due to any cause. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive.

Measure: OS(Overall Survival)

Time: up to 24 months

Description: To evaluate the effectiveness of Anlotinib Hydrochloric Capsule Plus Icotinib Hydrochloric Tablet by enhanced CT/MRI scan every two cycles. Objective Response Rate (ORR) is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients.

Measure: ORR(Objective Response Rate)

Time: each 42 days up to intolerance the toxicity or PD (up to 24 months)

Description: To evaluate the effectiveness of Anlotinib Hydrochloric Capsule Plus Icotinib Hydrochloric Tablet by enhanced CT/MRI scan every two cycles. Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease).

Measure: DCR(Disease Control Rate)

Time: each 42 days up to intolerance the toxicity or PD (up to 24 months)

Description: Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Measure: Adverse Events

Time: Until 30 day safety follow-up visit

11 Prospective Observational Trial to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Epidermal Growth Factor Receptor(EGFR)-Mutation

The third generation epidermal growth factor receptor-tyrosine Kinase Inhibitor(EGFR-TKI) osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

NCT04184921 Lung Cancer Non-small Cell Stage IV Drug: Aspirin 100mg Drug: Osimertinib 80 MG
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---

Primary Outcomes

Description: To evaluate the response to therapy and progression-free survival rate of the combination of Osimertinib and Aspirin in advanced lung cancer patients who has EGFR-mutation.

Measure: progression-free survival rate according to resist 1.1

Time: 2 years

Secondary Outcomes

Description: To evaluate the overall survival of the combination of Osimertinib and Aspirin in advanced lung cancer patients who has EGFR-mutation.

Measure: overall survival(OS)

Time: 5 years

Description: To evaluate the response to therapy and Objective Response Rate of the combination of Osimertinib and Aspirin in patients who has EGFR-mutation.

Measure: Objective Response Rate(ORR) according to resist 1.1

Time: 2 years

Description: To evaluate the response to therapy and Time to progression of the combination of Osimertinib and Aspirin in patients who has EGFR-mutation.

Measure: Time to progression(TTP) according to resist 1.1

Time: 2 years

12 Phase I Study to Evaluate Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of WSD0922-FUFU

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

NCT04197934 Anaplastic Astrocytoma, IDH-Wildtype Glioblastoma, IDH-Wildtype Lung Non-Small Cell Carcinoma Metastatic Malignant Neoplasm in the Central Nervous System Metastatic Malignant Neoplasm in the Leptomeninges Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU Procedure: Therapeutic Conventional Surgery
MeSH:Glioblastoma Astrocytoma Neoplasms, Second Primary Carcinoma, Non-Small-Cell Lung Neoplasms
HPO:Astrocytoma Glioblastoma multiforme Neoplasm Non-small cell lung carcinoma Subependymal giant-cell astrocytoma

Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than three years prior to registration - Any of the following cardiac criteria: - A marked baseline prolongation of QT/corrected QT (QTc) interval - (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fridericia's QT correction formula - A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome) - The use of concomitant medications that prolong the QT/QTc interval - Patients confirmed to have a cis double mutation (Del19/T790M or L858R/T790M) or cis triple mutation (Del19/T790m/C797S or L858R/T790M/C797S) - Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. --- T790M --- --- L858R --- --- C797S ---

Primary Outcomes

Description: The RP2D is either the maximum tolerated dose (MTD) or the highest dose tested (in the case that none of the doses are deemed higher than the MTD), whichever is higher.

Measure: Recommended phase 2 dose

Time: Up to 28 days

Secondary Outcomes

Measure: Incidence of adverse events

Time: Up to 4-6 weeks after study completion

Description: The overall response rate will be defined as the number of patients with a partial response (PR) or better that is confirmed in consecutive evaluations (at least 8 weeks apart) divided by the total number of evaluable patients. A 95% confidence interval will also be constructed using the properties of the binomial distribution.

Measure: Overall response rate

Time: Up to 5 years

Description: Duration of response is defined as the number of days between a patient's first occurrence of a PR (or better) and progression. If a patient goes off study prior to progression (for another reason) then they will be censored at that time. A time to event analysis will be performed utilizing the Kaplan-Meier method which will yield a median DOR.

Measure: Duration of response (DOR)

Time: From the first occurrence of a PR (or better) and progression, assessed up to 5 years

Description: A patient's progression free survival time is the number of days between study entry and disease progression. These data will be analyzed utilizing the Kaplan-Meier method which will yield a median PFS time.

Measure: Progression Free Survival (PFS)

Time: From study entry to disease progression, assessed up to 5 years

Other Outcomes

Measure: Maximum plasma Concentration [Cmax] of WSD0922-FU after a single dose of WSD0922-FU

Time: Cycle 1 Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours

Measure: Area under the plasma concentration versus time curve (AUC) of WSD022-FU after a single dose of WSD0922-FU

Time: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours of day 1 of cycles 1 and 2; and pre-dose day 1 of cycles 3 and 4

Measure: Maximum plasma Concentration [Cmax] of WSD0922-FU after multiple doses of WSD0922-FU

Time: Cycle 1 Day 15: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours

Measure: Area under the plasma concentration versus time curve (AUC) of WSD022-FU after multiple doses of WSD0922-FU

Time: Cycle 1 Day 15: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours

Measure: CSF concentration of WSD0922-FU after multiple doses of WSD0922-FU (Dose Expansion - NSCLC leptomeningeal metastases (NSCLC LM) cohort only).

Time: Cycle 2 Day 1

Measure: Brain tumor concentration of WSD0922-FU after a single dose of WSD0922-FU (Dose Expansion - Brain tumor penetration (BTP) cohort only).

Time: Cycle 0 Day 1

Measure: Tumor EGFR inhibition after a single dose of WSD0922-FU (Dose Expansion - Brain tumor penetration (BTP) cohort only).

Time: Cycle 0 Day 1

Measure: Effect of food on Maximum plasma Concentration [Cmax] of WSD0922-FU after a single dose of WSD0922-FU (Dose Expansion - NSCLC LM cohort only).

Time: Cycle 0 Day 1 and Cycle 0 Day 4

Measure: Effect of food on Area under the plasma concentration versus time curve (AUC) of WSD022-FU after a single dose of WSD0922-FU (Dose Expansion - NSCLC LM cohort only).

Time: Cycle 0 Day 1 and Cycle 0 Day 4

13 MasterKey-01: A Phase 1/2, Open-label, Two-part, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics & Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB Mutations, in Patients w/ Advanced Solid Malignancies

This is a clinical study with an orally administered drug, BDTX-189 in participants with advanced solid tumors that have select mutations or alterations in human epidermal growth factor receptor 2 (HER2/ErbB2) genes or epidermal growth factor receptor (EGFR/ErbB1). The main goals of this study are to: - Find the recommended dose of BDTX-189 that can be given safely to participants - Learn more about the side effects of BDTX-189 - Learn what the body does to BDTX-189 after it has been taken (pharmacokinetics or PK) - Determine the antitumor activity of BDTX-189 in participants with select allosteric ErbB gene mutations

NCT04209465 Solid Tumor Drug: BDTX-189

Evidence of second- or third-degree atrioventricular block 2. Clinically significant arrhythmia (as determined by the Investigator) 3. QTcF interval of >480 msec - Leptomeningeal or untreated and/or symptomatic CNS malignancies (primary or metastatic) - Women who are pregnant or breast-feeding - Taking or unable to discontinue proton pump inhibitors within 1 week prior to baseline Phase 2 Only: - Prior documented treatment response to approved or investigational HER2 or EGFR tyrosine kinase inhibitor therapies - Known concurrent KRAS mutation - Known tumor-harboring resistance mutations including EGFR T790M or C797S mutations or HER2 C805S mutation Main Inclusion Criteria: - Histologically- or cytologically-confirmed locally advanced or metastatic solid tumor with documented recurrence or disease progression from standard anticancer therapy in the advanced/metastatic setting - No standard therapy available or standard therapy is considered unsuitable or intolerable according to the Investigator and consultation with the Medical Monitor Phase 1 Only: - Solid tumor patients with alterations that may be associated with antitumor activity based on preclinical data for BDTX-189 such as: 1. Allosteric HER2 or HER3 mutation(s) 2. EGFR or HER2 exon 20 insertion mutation(s) 3. HER2 amplified or overexpressing tumors 4. EGFR exon 19 deletion or L858R mutation Phase 2 Only: - Patients with a solid tumor harboring an: 1. Allosteric HER2 mutation (including but not limited to S310F/Y, R678Q, L755S/P, V777L, V842I) 2. EGFR or HER2 exon 20 insertion mutation Eligible mutations must be determined by a validated next-generation sequencing (NGS) test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory. --- T790M --- --- C797S ---

Evidence of second- or third-degree atrioventricular block 2. Clinically significant arrhythmia (as determined by the Investigator) 3. QTcF interval of >480 msec - Leptomeningeal or untreated and/or symptomatic CNS malignancies (primary or metastatic) - Women who are pregnant or breast-feeding - Taking or unable to discontinue proton pump inhibitors within 1 week prior to baseline Phase 2 Only: - Prior documented treatment response to approved or investigational HER2 or EGFR tyrosine kinase inhibitor therapies - Known concurrent KRAS mutation - Known tumor-harboring resistance mutations including EGFR T790M or C797S mutations or HER2 C805S mutation Solid Tumor BDTX-189 is an irreversible, small molecular inhibitor that is highly selective versus wild-type EGFR and potent for cancer driver mutations of the ErbB family, including extracellular, transmembrane, and kinase domain allosteric mutations of HER2, as well as EGFR and HER2 exon 20 insertion mutations. --- T790M --- --- C797S ---

Primary Outcomes

Description: Certain toxicities will be considered dose-limiting unless clearly attributable to an extraneous cause, such as underlying disease.

Measure: Incidence of dose limiting toxicities as a determinant of the Recommended Phase 2 Dose (RP2D)

Time: After the first dose of treatment for up to 21 days.

Description: Objective response rate is defined as the proportion of participants who achieve a confirmed complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1.

Measure: Phase 2: Objective response rate as a measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Secondary Outcomes

Description: Adverse events will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Measure: Phase 1 and Phase 2: Incidence of treatment-emergent adverse events as a measure of safety and tolerability of BDTX-189

Time: From Cycle 1 Day 1 (each cycle is 21 days) until 30 days post last dose

Description: Blood samples will be taken to measure the plasma concentrations of BDTX-189 in both a fed and fasted state.

Measure: Phase 1 and Phase 2: Plasma concentration of BDTX-189 as a measure of pharmacokinetics

Time: Multiple time points during Cycles 1-4 (each cycle is 21 days)

Description: Objective response is defined as the proportion of participants who achieved a complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1.

Measure: Phase 1: Objective response rate as a preliminary measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Description: Duration of response is the time from first documentation of a response to first evidence of progressive disease per RECIST version 1.1 or death. A response is defined as either a complete response (CR; disappearance of all target lesions and non-target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions). Progressive disease is defined by a target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions.

Measure: Phase 1 and Phase 2: Duration of response as a measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Description: Disease control rate is defined as the proportion of participants achieving: a complete response (CR; disappearance of all target and non-target lesions), partial response (PR; at least a 30% decrease in the sum of diameters of target lesions), or stable disease (SD; neither sufficient shrinkage to qualify for a PR nor sufficient increase in lesions) per RECIST version 1.1.

Measure: Phase 1 and Phase 2: Disease control rate as a measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Description: Progression-free survival is the time from first study dose until disease progression (PD; target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions) per RECIST v1.1.

Measure: Phase 1 and Phase 2: Progression-free survival as a measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Description: Overall survival is the time from first study dose until death from any cause or study discontinuation.

Measure: Phase 2: Overall survival as a measure of clinical activity

Time: Assessed every 12 weeks after treatment discontinuation for up to 1 year


HPO Nodes


HP:0002664: Neoplasm
Genes 1515
EPCAM BAP1 CYLD WT1 CTBP1 GLI3 CTNNB1 ELMO2 ATRX TERT EDN3 MTAP TSC2 RAD51 BLNK KCNAB2 WDPCP SPINK1 ARID1B PTEN STK11 XPA PTH1R TCF4 EPCAM NF1 GPC3 ERCC3 MC1R CASP10 PDGFRA RPL5 CDH1 BRIP1 RUNX1 KRAS SFTPC GPR35 MYLK STS DYNC2LI1 RAG2 CBL FOXE1 STAT3 TTC37 ABL1 NSD1 ATM KCNH1 GPR101 IGH KRT17 SUFU TERT KRAS GPC3 CYP11B2 MLH3 PTCH1 FAH MSH2 EXT1 CCND1 MSH3 ATP7A SEC23A PHOX2B HAX1 MYD88 LMO1 PIK3CA PRLR AXIN1 TCF4 RUNX1 AKT1 ERBB2 REST DCLRE1C SERPINA1 ERCC3 TMC6 RASA1 MSH3 TRNL1 CALR HRAS INS RNF113A SETBP1 CDH1 SLC37A4 TFAP2A CDH1 PTCH1 KIT PTEN IL1RN MLH3 MUTYH PTEN KIT GBA BCL2 KCNH1 GINS1 ESCO2 TET2 SLX4 DICER1 PALB2 NEK1 ESCO2 COL7A1 PTCH2 WT1 WRN GCM2 BRD4 BRAF TREX1 THPO SUFU NRAS CDC73 POU6F2 GNAS DAXX BUB3 RSPO1 MNX1 ERCC2 RPS28 ANTXR2 CTNNB1 POT1 FANCA KDM6B RET MST1 NOTCH3 FGFR1 KRAS LYST CHIC2 TMC6 MET KRT10 UROD SLC25A11 ARSA EVC2 TEK XRCC2 CASP8 ASCL1 IL1B TERF2IP DICER1 MPL OFD1 RHBDF2 DICER1 MDM2 WT1 MMP1 CDKN2A FGF8 NR4A3 FGFR2 OCRL TP53 ERCC2 SUFU ERCC4 ALX4 TINF2 DCLRE1C SRY SRP72 NF2 GNAS LETM1 TP53 FANCB TAL1 TDGF1 BRCA1 LEMD3 NF2 BRAF NUP214 RAD21 COL18A1 SDHD ICOS CEP57 BAP1 FANCM PTPRJ FANCE SLC22A18 PIK3R1 JAK2 FLT4 SMO WIPF1 DLST NF2 RAD50 MEN1 CHEK2 GPC4 WDPCP CYP2A6 HBB GANAB XRCC4 TET2 ATP7B EP300 DIS3L2 HFE CARD14 OFD1 ALX3 VANGL1 BAP1 SDHB EXTL3 PIK3CA GATA2 ALX3 BCL10 KIT WAS FGFR2 RMRP TWIST1 BMPR1B DIS3L2 ERCC3 FOXP1 SMAD4 CALR APC PCGF2 USP8 DMPK NRAS DKC1 BRCA1 ADAR BCR RSPO1 SLC45A2 GJC2 TNFRSF4 AKT1 IFIH1 MSH6 DICER1 PAX6 TGFBR2 SRY KLHDC8B CPLX1 MSH6 AIP PMS1 CREBBP ERCC2 CTSA APC MMP1 SH2B3 PKD1 TRNF SEC23B DNAJC21 STK11 BCR HBB MITF IGLL1 ALX4 MDH2 AKT1 SCN4A SDHAF2 PRKN PLA2G2A RNF43 DNMT3A TERT NSD2 RMRP FANCG BRCA2 CAT TP53 BMPR1A MAD2L2 SIX6 DDB2 GREM1 KRT17 PAX4 RPS17 TRPV3 ERCC4 C11ORF95 APC IL12RB1 BRIP1 PPM1D SDHB NODAL HNF1A FLT4 MSH6 ERCC6 BTK SLC26A4 SEMA3C AR NEK1 TERC RPL35A RPS20 CDKN1C SF3B1 TERC PTEN RFWD3 BRCA2 KCNQ1OT1 RPL10 ACTG2 MAGT1 ALK BLM H19 LEMD3 RPL31 MLLT10 PYGL RPL15 IRF1 CR2 MITF PTEN MYC PTPN11 TUBB TCF4 KCNQ1 NFKB2 ALX1 HLA-DRB1 APC EWSR1 NBN CDKN2A ERCC4 GCK DLL1 SLC25A11 PDGFB L2HGDH PRKCD CTC1 PIK3CA SUFU RPL27 KIF1B SRC CIB1 RECQL4 CDKN2B MSH3 BRCA2 PALB2 PDE6D SDHC SDHD CCL2 CHEK2 PMVK XPC STK11 PIK3CA MVD DHCR7 KIT GPC6 KARS1 MNX1 VHL TUBB NAB2 KEAP1 TSC1 NQO2 APC SDHB VHL TCTN3 RECQL4 PMS2 RAD51C STAG3 SNAI2 MAP3K8 SETBP1 SDHB NPM1 RAD51C RARA ERBB2 ERCC5 ATRX CHEK2 KRAS BRCA1 TFAP2A SLCO2A1 PHOX2B PTEN COL2A1 PIGL PDGFRA APC CPLANE1 AURKA SDHD LAMA3 VHL RPS26 GFI1B CDKN1B PRDM16 AXIN2 FZD2 AP2S1 LZTR1 TP53 TP53 GNA14 CTNNB1 MSTO1 PIK3CA RPS29 CALR DHX37 MYF6 SDHC MALT1 ELANE SDHD SLC26A4 MAP3K1 GDNF MSH2 SDHC TGFBR1 RUNX1 CREB1 CDKN2A TSC2 KRAS TNFRSF10B LMNA WWOX PHOX2B EDN3 RPS10 RSPRY1 TRIM37 RET MEN1 BCL10 MSH2 TNFRSF13C FOXE1 FANCC H19-ICR BLM ERCC6 LIG4 BDNF LMOD1 NF2 TMEM107 CYLD GJB2 EXT1 CTSC PHOX2B RAD51D RASGRP1 RB1 TGFBR2 SRY MYH8 KRAS TINF2 RECQL4 H19 PRF1 GDNF MXI1 SMPD1 WT1 HRAS COL1A1 PDGFRB FAS FANCD2 NF1 DISP1 PDGFRL IKBKG BIN1 BRCA2 ADA POLE AXIN2 SEMA4A KRAS NRAS PALB2 CHEK2 ASCL1 POLE TLR2 PIK3CA MINPP1 SOS1 CYLD CTLA4 POT1 ASXL1 CDC73 APC SAMD9L WT1 TRAF7 GATA4 PIK3CA DYNC2LI1 ATP7A CBFB MST1R GCGR MPL COL4A5 SMAD4 CDKN1A SDHD TRIM28 POLH GPR101 PIK3CA FLCN GPR143 RB1 SBDS SLC12A3 KLF6 ICOS GNB1 PIGA TYROBP GFI1 RAD51 SLC26A2 MC1R TREM2 SFTPA2 JAG1 BAP1 EGFR IGH KIT PLCB4 NLRP1 HNF1B ZFHX3 EPHB2 KLLN OCA2 WT1 FAH FH TERT SRD5A3 LIG4 NFKB1 RNF43 KIT STAT1 IFNG BMPR1A ERCC3 TBX18 TET2 MAP2K1 EXT2 HRAS RTEL1 FGFR3 PTEN CTNNB1 MAP2K2 MEN1 APC CLCNKB AKT1 ESCO2 CDC73 MS4A1 BRAF CRKL NUTM1 CDK4 NTHL1 ETV6 TET2 SQSTM1 FAM20C PIGL SEC23A ATM PALB2 TYR SRSF2 EXT2 GJB2 DNMT3A HRAS TCOF1 CHEK2 CDH1 FH DKC1 POLE PIK3CA PTCH2 AKT1 PAX3 FH ADAMTS3 APC PMS1 RAD51C PLCD1 PUF60 DIS3L2 CDH23 SCN9A FOXC2 SMARCB1 CDKN2A VANGL2 ENG SH2D1A SDHB SOX9 BRAF SDHA PGM3 ERCC2 GJB2 TBC1D24 CHD7 MPL DHH PTCH1 CALR IL12A TNFRSF13B CD28 MLH1 PTPN12 OFD1 MLH3 REST CCDC22 APPL1 COL14A1 IGH PSENEN IL2RG MC1R SMARCA4 CYLD KIF11 PHKG2 JAK2 COL2A1 AXIN2 FLNA WNT5A TYR EP300 GLI3 EXT2 MGAT2 KCNE3 ECE1 PARN IDH2 TSC1 ARL6IP6 FGFR3 SMAD4 HMBS SLC6A17 PRKAR1A BAP1 KDSR DHCR24 CXCR4 DDX41 GABRD RET NR0B1 DMRT3 CCND1 GDF5 POU6F2 CTLA4 TBXT FANCA NRTN PHKA2 KIT ITK RNASEH2A PERP CDC73 OFD1 CYP2D6 RET MEN1 CD27 PARN FUZ RPS19 MSH2 SMARCE1 TNFSF12 ZSWIM6 TERT RHOH NF1 BUB1B SLX4 LIG4 PDGFRL TNFSF15 OPCML APC PRKCD SETD2 RPS19 BRCA1 FAT4 ANTXR1 WNT10A SUFU TP63 EFL1 IL7 MN1 DOCK8 CDC73 SSX1 TMEM231 MPLKIP VHL MINPP1 BIRC3 PDX1 STS PSAP HNF1A JAK2 FANCL POT1 GNAS TERT CD79A KLF11 WRN MAPRE2 LIG4 CYSLTR2 DNM2 SH3GL1 KIT FOXH1 RELA KRAS PRKAR1A ERBB3 FGFR2 H19 TJP2 CD81 PNP MSH6 WT1 THPO ATP6V1B2 GNAQ BRCA1 WRAP53 ERCC3 CHRNG KRT14 TSC1 DLC1 CTNNB1 FGFRL1 SDHC GDNF HABP2 NRAS ATR TRNK BMPR1A TERT BRAF AKT1 XPC FGFR3 NUP214 TRIP13 SMARCD2 ZSWIM6 PIEZO2 EVC IL6 HRAS GPC4 TNFRSF13B PALLD CDKN2A POLR1D TP53 FOXO1 BRCA2 FIBP CDH23 RB1CC1 B3GALT6 FLT3 GJA1 SH2B3 MRAP MTOR AR FOXI1 TP53 GNAQ KRT6B MYD88 KRT16 TP53 NF1 MYSM1 MGMT KIT NF1 GPC4 GCM2 SIX3 PIK3CA RAD21 HRAS PMS2 ASCC1 BRCA2 GAS1 FASLG SDHD NRAS C2CD3 KDR SDHA SMAD4 SOX2 NBEAL2 SRGAP1 AGGF1 ATM AKT1 RPGRIP1L NOD2 BAX BRCA2 H19-ICR TGIF1 MAPK1 ESR1 EXT1 RPL11 KRAS BCL10 SKI LAMB3 XIAP SDHC HABP2 TRNS1 CCM2 FIBP PIK3CA TRIM28 HRAS SCN10A NF1 WT1 CPLANE1 HFE F5 C2CD3 GNPTAB TBX2 KLF6 GATA2 VEGFC RNASEH2B CBL SEMA3D ARMC5 CXCR4 JAK2 IGF2 FGFR2 NRAS UBE2T ARHGAP26 SCN11A MEN1 LMX1B F13A1 BCR COMP EDN1 SDHC ACTB GDNF CDKN2C ASPSCR1 NAGS PDGFRB PALB2 DLEC1 BCL10 STAR GNA11 PORCN RNR1 FLCN SPIB WT1 RET SDHB SLC22A18 ERCC4 CDKN2A CTHRC1 DLST OGG1 POLD1 DCC IL2RG REST SRP54 RAF1 TSC1 SRP54 IDH1 ACD KIT ACAN NSD2 TOP2A CASP10 DVL1 PTPN11 CASP10 STIM1 KRT9 AR CIB1 GNAS AR VAMP7 MRE11 GFI1 RPS14 BCL10 CACNA1S TP53 VANGL1 SKIV2L PTCH2 G6PC LRP5 PDGFRB BARD1 RPS27 RPS7 GNAS ENPP1 STAT6 ACVR1 MTM1 NEUROD1 TNFRSF13C PKD2 RUNX1 STK11 FGF3 TRIP13 SIX1 BRCA2 LAMC2 NELFA DVL3 GJB4 NSUN2 CDKN1B CTNNB1 POLR1C GJB3 SMARCB1 SBDS LMNA KRAS TRNH ECM1 STK4 ANTXR2 SOS1 BAP1 MSX2 DICER1 SDHB ACD WRAP53 BRCA1 ATP7A BUB1B RYR1 RET BRCA2 TP53 DPM1 BRCA2 BCR POLD1 TCIRG1 PTPN11 HOXD13 CR2 TARS1 JAK2 BMP2 MUTYH FLT3 TRNS2 MTMR14 NR5A1 ABCA5 RET AHCY TSC2 KIT KCNQ1OT1 RNF6 RAD54L HNF1A HMMR RNF139 WWOX TCTN3 BRAF FCN3 RNASEH2C AIP PRKN SF3B1 MSH6 NSD1 PTCH2 CCBE1 RECQL4 PMS2 ERCC2 HNF4A MMEL1 BUB1 TET2 TRPS1 ABCC6 RET IRF5 CDKN2B PDGFB USP9X TAL2 INTU GNAS HDAC4 MFN2 DYNC2H1 PIK3CA PLAG1 ATM MAX FAS PIK3CA CYP11B1 CCND1 H19-ICR PTCH1 MUTYH ABL1 ODC1 FGFR2 COL7A1 MSR1 BRCA1 RB1 TNFRSF1B COL7A1 FLT4 GPC3 TGFBR2 ATRX RAG1 PRCC BRAF TNFRSF1B FANCE RAD54L CBL SDHB TERT SDHD RPS24 FASLG MET KRT17 GATA1 ERBB2 FGFR1 KAT6B ABCA5 SDHAF2 SLC25A13 NOP10 GATA2 RFWD3 PDGFRA SPRTN MLH1 NKX2-1 IGF2R CD19 MAP3K1 TREX1 TRNP ZFPM2 CTNNB1 TRNQ WWOX IGHM MYH11 TMEM127 CDON NF2 SAMD9 PTEN RNASEL IDH2 HNF4A GTF2H5 GLI3 HRAS LPP DDB2 KIT PIK3CA PDCD10 HSPG2 HFE RPL26 BRIP1 ASXL1 SDHD CEBPA ACVRL1 NRAS CD19 GNAQ TET2 TCTN3 SMARCB1 FLCN ABCB11 BLK RAD54B SDHC FH AKT1 ANTXR1 FANCF HNF1B EXOC6B SAMHD1 SHOX MYO1H COL11A2 KCNJ10 TRIP13 CC2D2A LZTS1 SEC23B GPR101 DOCK8 BRCA2 NBN SLC26A2 SPRED1 VHL KRT1 LIN28B GTF2E2 NRAS ZIC2 SNAI2 SH3KBP1 SHOX BCL6 NTHL1 RHBDF2 CD28 MCM4 CCND1 FANCG SMARCAD1 GATA2 RERE YY1 ASXL1 IL7R TMEM67 C1S TAF1 FGFR3 NBN KRAS KIF1B AIP KCNJ11 LETM1 FANCI MLH1 MBTPS2 NRAS NEK9 GNAI3 APC2 EYA1 ZAP70 EXT2 BUB1 SSX2 LIG4 CARMIL2 SLC17A9 TMC8 PCNA EPAS1 TFE3 BRCA2 DHH MAP2K1 CASP8 CDK4 PDGFB RTEL1 EWSR1 PTEN VHL GJB6 NDP RNF6 TNPO3 TGFBR2 TXNRD2 PNP TAF15 TRNK SMO NOTCH1 LRRC8A RASA1 TSC2 ABCC8 PRKAR1A BAX IDH1 SLC22A18 ADA FAN1 TG PTEN BMPR1A MSTO1 ERCC5 IRF1 MLH1 NRAS MLH1 PICALM FANCD2 SF3B1 BICC1 RPS15A TERT KLLN ELANE FAM149B1 GATA1 SASH1 INPP5E TP53 WT1 BMPR1A PTPN11 PTPN11 MYCN XPA EDNRB TP53 FLI1 GDF2 PHB BMPER FGFR3 PTEN MCC EXT1 MC2R KCNN3 DNASE1L3 DHCR7 RASGRP1 SHH NPM1 SLC26A2 SLC37A4 IGF2 RPL18 SH2B3 PTCH1 BRAF PAX7 INHBA BMPR1A KIF7 XRCC3 IGF2 POU2AF1 DNAJC21 CYP26C1 RB1 MPL REST KIAA0753 DNMT3A ERCC6 MUC5B MLH3 ASXL1 MPL NOTCH3 KCNJ10 SMARCE1 TSR2 RPL10 KRT1 SLC25A13 WT1 NNT TP53 GNA11 GLI1 BARD1 FLCN COL7A1 SRP54 GLI2 EDN3 PTPN3 WT1 TMEM127 CD79B GATA2 TERC FN1 EIF2AK4 RAD51 WASHC5 SAMD9L AIP TP53 AAGAB RB1 TP53 KRT5 ADA2 HSPA9 PIK3CA SRSF2 PHF21A IDH1 KRAS KRAS CHEK2 BUB1B RET FANCC TP53 WHCR RAD54B NUMA1 SDHB HMBS TMEM216 SMAD4 MAFA MSH2 RPL35 CDKN1B IGF2 PPP2R1B CD70 CEL MAD1L1 MAX ALK GPC3 FERMT1 KIF1B TCF3 POLH PIK3R1 USF3 FDPS MYC DNAJC21 TNFSF12 HACE1 CDH1 SDHA ND5 NHP2 PIK3CA RPS14 NBN WNT10A ING1 CASR SUFU FGFR3 HPGD BTK ENG DCC CASP8 PHOX2B STAC3 USB1 KRIT1 PHOX2B TET2 SMAD4 JAK2 BCHE APC MVK SMAD7 SMO DKC1 SMARCB1 VHL F13B TINF2 USP8 FGFR1 FOXI1 TET2 CD96 TET2 JAK2 KRAS