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) and recommended Phase 2 combination dose (RP2CD) (combination therapy) in participants with advanced non-small cell lung cancer (NSCLC).

NCT02609776 Non-Small-Cell Lung Cancer Drug: JNJ-61186372 Drug: JNJ-61186372 Drug: Lazertinib
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 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 End of Treatment 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 End of Treatment Follow Up Period (30 [+7] days after the 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:Adenocarcinoma 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 1489
WHCR ATP7A PHOX2B KRT17 IL2RG HMGA2 PORCN KRAS TET2 IDH2 FLT3 ERCC4 AR BRCA1 BRCA2 GATA1 TCF4 TCTN3 GPR101 SMAD7 KRT6B PIK3CA KCNJ10 MAP2K2 REST TTC37 MC2R TRPS1 SIX6 ALX4 PIK3CA BRAF TP53 STK11 TSR2 EXT2 EDN1 RNF43 TRNL1 ATM SDHC EXT1 BCL10 BAP1 NF1 OCRL TP53 CHD7 TINF2 ERCC6 NF1 MAFA PMS2 ASXL1 PHOX2B CTNNB1 CR2 RET TCTN3 C11ORF95 PTPN3 PIEZO2 ABCB11 SETBP1 PDCD10 LRP5 LMOD1 MALT1 ASXL1 LZTR1 TINF2 RAD51C RECQL4 MAP2K1 FOXO1 PTCH2 RPS20 FLI1 BMPR1A SMARCAD1 BMPR1A MAP3K8 DNASE1L3 SUFU TP53 FOXP1 PTCH1 PDGFRB ND1 PIK3CA ZSWIM6 SETD2 INS NRAS HBB MEN1 AIP CLCNKB RPS10 HFE COX2 TSC2 DHH CTRC MEN1 EYA1 BRCA1 GINS1 MSH3 GLI2 TRNS1 HABP2 SSX1 SUFU PRKN CD81 TNFSF12 MYH11 KIT VEGFC WWOX H19 SDHD FGF3 TNFRSF1B RMRP XRCC2 HRAS MTM1 EPHB2 PLCD1 NBN CDKN1B TUBB RECQL4 EDNRB VHL ACAN MSH6 CDKN2B DCC TJP2 HRAS CDKN2A VHL REST NKX2-1 ANTXR1 RPL35 DNM2 FGFR3 SNAI2 NLRP1 ACTG2 GNB1 EWSR1 CBFB NSD1 FLCN ERBB2 MLH1 H19 EIF2AK4 RPL10 TMEM107 TRNK RAD54L RAD51C INPP5E NFKB1 CDKN1A KDM6B F13B SLC26A2 TRNS1 RPL26 CYLD H19 PTEN PTPN11 DCLRE1C MPL FLCN NEK1 MITF MSH3 NUTM1 IL7 STAT3 TRNS2 TG ERCC3 MNX1 NRAS MLH3 TSC1 GLI3 CDK4 SDHC NF1 BRCA2 CIB1 ATRX BRCA2 ADAMTS3 ZFPM2 COL2A1 TET2 ZIC2 SLCO2A1 BLM GJA1 MAP3K1 PIK3CA SDHA RTEL1 CDK4 KCNH1 SH2B3 APC ESCO2 FANCC TERT USP9X APC RAD54B NF2 SDHB RPS14 PPP2R1B RPS19 RPL35A MSH2 WRAP53 RASA1 LMNA ACVRL1 POLH SDHB DIS3L2 PIGA GNPTAB CXCR4 MSH2 SLC25A13 BMP2 NNT PSENEN FOXI1 APC IL1RN MITF ACD PTEN MPL RUNX1 ERCC3 ERCC4 DLEC1 CHEK2 BRCA2 JAK2 SBDS BRCA1 SDHD SEMA3D MSH6 HFE TREM2 APC CCDC22 MINPP1 DISP1 FAM20C MAP2K1 ALK BRCA1 STIM1 SLC25A13 RFWD3 HRAS GLI1 TET2 DVL3 COL7A1 HMBS TFAP2A ICOS CALR PTEN UROD DKC1 FDPS LIG4 TXNRD2 SRSF2 ND5 SDHD CHEK2 NRAS BCL6 GPC3 XPC MEN1 ERCC2 AXIN2 MYC RAD51 GBA KIF1B SDHB EXT2 EXT2 NTHL1 SRY RPGRIP1L MPL MTOR CASP8 RB1CC1 IGF2 FANCC ERCC4 WRN PGM3 VHL ING1 PLAG1 WT1 MYLK KLLN PIK3CA G6PC RPS7 MCM4 ANTXR1 POLH BRCA2 DLL1 OGG1 WRN F13A1 SBDS EFL1 TAF15 GLI3 GPC3 KRAS CDKN2B MAPK1 DIS3L2 GPR101 NRTN DKC1 KLLN NSUN2 MAP3K1 ERBB2 PHKG2 SRGAP1 CYLD NBN ALK MAX WT1 ACTB PALB2 TBX18 FIBP CASP10 DVL1 TYR MSH2 RECQL4 PIGL EDN3 WT1 ATP7B RPL27 RET USP8 FGFR2 PDGFRL H19 CCND1 ATM AXIN2 COL7A1 AKT1 TERT MUTYH HOXD13 DICER1 THPO GDF5 CEL SDHB EXT2 SRP72 TERT TRNF TP53 LIN28B APC NPM1 FGFR3 PTEN SMPD1 SLC22A18 SDHC PRDM16 KIT STK11 RPL11 LETM1 CALR SDHC RB1 PIK3CA PLCB4 COL4A5 CASP8 SKI H19 COL1A1 CC2D2A CASP10 GCGR GLI3 PIK3CA RPS29 RSPO1 PTEN MYSM1 BAP1 SRY UBE2T BRCA1 USP8 COL7A1 RNASEH2B KIF1B MN1 RELA SMAD4 VHL SH3KBP1 BCR CD79B SRP54 SRP54 SSX2 CHRNG RPL18 NF1 WWOX RERE LZTS1 WT1 MSH3 TYROBP ASCL1 IKBKG ABCC6 FAH KIT GDNF FANCE TERT BIN1 FANCL KIF11 SDHB WDPCP SLC6A17 TP53 HNF1A KEAP1 POLE HSPA9 SMO PTCH2 PTCH1 PMS1 ELMO2 BCL2 NSD2 EXT1 SRD5A3 STAT6 MVD TERC SF3B1 MNX1 FGFR1 CYSLTR2 POU2AF1 SMARCB1 NOD2 GJB2 SDHC FLT4 KRT9 CDH1 IRF1 SEC23B MYCN MGMT RPL10 RPL5 KIF7 TCF3 KRAS MUTYH TMEM127 KRAS IGH CTSC GNAS CD28 WWOX HNF1A BUB1B MC1R WNT10A CBL WT1 BRAF ADAR GAS1 GTF2E2 SMARCB1 RPS17 PARN TMEM127 BRIP1 SHH SRC GNAI3 STAR GDNF SLC22A18 FOXH1 SNAI2 GPC4 TNFRSF13C KARS1 TBC1D24 BMPR1A TET2 CD27 CASP8 DHCR7 KDSR HNF1A SH3GL1 PNP USB1 TSC2 TRIP13 TMEM67 EDN3 PMS1 PTPN11 GNA11 CREB1 ADA RAG2 PRSS1 KCNQ1 GPR101 PRF1 MTAP FANCA MSH6 TRNQ BRCA2 KRT1 RNASEL POU6F2 ACD SCN9A APC NSD2 INTU BRAF POU6F2 BRCA2 RB1 GTF2H5 PIK3CA FANCM TARS1 BRAF CASR RET VHL GPR143 TRNP GCM2 TMEM231 CPLANE1 RPS15A SOX9 GFI1B EPCAM MEN1 TERT KRAS SDHAF2 NF1 TRIP13 GATA2 SLC26A4 APC MPLKIP SAMD9L IL6 GNAS IGH AKT1 FANCD2 ESR1 SDHA APC MYF6 RASGRP1 SMAD4 MLLT10 LIG4 CPLANE1 BRCA2 MC1R MRE11 DLST SUFU LMO1 SDHB ABCA5 RMRP SDHC NUP214 AKT1 SMARCD2 DLC1 C1S TRNW THPO CHEK2 KIT SLC37A4 BCHE KCNJ11 ARID1B APC2 SAMD9 TMC6 SLX4 TNFRSF13B FGFR1 TRNH RAD21 KCNN3 DKC1 VANGL1 AXIN2 TCOF1 RPS19 SLC26A2 GPR35 CR2 TFAP2A KRAS FGFR3 PRKCD JAK2 EGFR AIP CTNNB1 KCNJ10 FANCI LYST TET2 SLC25A11 TP53 TCTN3 MUTYH ANTXR2 SEMA3C MMP1 AKT1 PDX1 JAK2 TCIRG1 PTCH1 MUC5B EXT1 DNMT3A BMPR1A SERPINA1 FAN1 CDC73 PTCH2 PIK3CA H19 FERMT1 GPC3 RET RET APC PALLD LPP BRD4 GNAS BMPR1B MAPRE2 DICER1 CTC1 TAL1 DICER1 STK11 HRAS GATA1 BCL10 KCNE3 XRCC4 HNF4A BDNF KLF11 SF3B1 MLH3 GNAQ TRPV3 IGLL1 PAX7 CRKL GDNF GATA2 ARL6IP6 ENG PTCH1 NEK9 TSC1 RNF139 ERCC3 PDGFRA IL2RG CTHRC1 WT1 BAP1 ATP7A SRP54 ABCC8 ESCO2 GPC4 OFD1 TNFSF15 APPL1 RNF6 CTSA TNFRSF1B TP53 PHOX2B DCLRE1C DDB2 BCL10 BCR KRT14 ALX3 EVC2 CD70 SMARCB1 AHCY SDHAF2 RAD51D SPINK1 SDHD ATM GABRD WT1 FASLG CTBP1 NOTCH1 NF2 DPM1 ERCC6 STS PHOX2B BUB1 FLT4 L2HGDH LAMC2 NTHL1 STAG3 ENG SDHD CTNNB1 DAXX NRAS MST1 MSTO1 SLC26A4 RAF1 STS FGFR3 EXOC6B VAMP7 NELFA HRAS ANTXR2 LEMD3 TNFSF12 GPC4 MLH1 SMAD4 RAD50 SUFU TRIP13 REST GNAS CBL RHBDF2 ASXL1 SMAD4 TCF4 ERCC6 WT1 BRAF APC TRIM28 TERT DNAJC21 RPL15 PAX3 SETBP1 CDH1 GNAS SMARCB1 AKT1 ASCL1 KRAS NAB2 ERCC5 RECQL4 KRAS DNMT3A EDN3 POLD1 FAM149B1 CDKN1C KRAS TP53 SMARCE1 PTEN PALB2 SEMA4A TEK NBN NHP2 GPC3 ETV6 FGF8 COL11A2 SMAD4 RNASEH2A NRAS MC1R TDGF1 FGFRL1 FGFR1 CTNNB1 IGH DNAJC21 CCND1 RET DIS3L2 DHCR24 CARD14 BRCA2 SQSTM1 NFKB2 TRNQ NDP SFTPA2 PAX4 COL7A1 TP53 RSPRY1 IFNG HMMR PALB2 FAT4 MBTPS2 MDM2 KRAS GNAS C2CD3 POT1 ABL1 WNT5A FANCE ABL1 ICOS SDHD RAD21 NSD1 SOS1 IL12A LIG4 PIK3CA TBXT RAD51 EWSR1 FZD2 FLNA BRCA2 NRAS TWIST1 TET2 TSC1 INHBA CAT CTNNB1 PIGL IRF1 PTCH2 TRNH MLH1 GFI1 CDC73 RET FANCD2 EVC NF2 TNPO3 SOX2 DYNC2H1 HRAS NEK1 CCND1 KRT10 AKT1 KIT PALB2 VHL CYLD IL1B GJC2 MLH1 SDHC FGFR2 CYP2A6 FOXE1 ARMC5 ERCC2 SLC25A11 LAMA3 FLCN BRCA1 BIRC3 MVK TOP2A PDGFB TCF4 RFWD3 ATP6V1B2 GDNF GATA4 CTNNB1 CDKN1B C2CD3 BRCA2 FUZ STK11 AKT1 FGFR2 SHOX TGFBR1 BTK LEMD3 FIBP SF3B1 SUFU PRLR NR5A1 FN1 ERBB2 CD19 RNR1 PTPN11 KIT RAD51 WAS PTEN TGFBR2 RPS24 CYLD RNF113A MYO1H ALX3 JAK2 BLM CTNNB1 CDKN2A PARN SH2B3 POLD1 CHEK2 COX1 KRT1 EXT1 BRAF PRCC MSH2 GATA2 REST NRAS RB1 TINF2 BMPR1A NR4A3 AGGF1 SIX3 RAG1 ND4 COL2A1 CDKN2A SDHD TREX1 WNT10A SEC23B XPA MET TP53 CDKN1B RPS27 PCNA HMBS RPS26 KIT FGFR2 TRIM37 HPGD ERCC5 PAX6 SLX4 PICALM PSAP FCN3 BMPR1A USF3 XPC DNAJC21 KRT16 BUB3 H19-ICR GPC6 STAC3 RPS28 FANCA RNF43 AP2S1 PDGFB DYNC2LI1 CYP11B1 ABCA5 PTCH1 TERF2IP KRAS DYNC2LI1 CDH1 CDC73 TERC SPRED1 PDGFB TRNF MTMR14 MAD2L2 FOXI1 ERCC2 GJB4 KAT6B MSH6 FASLG KRAS SEC23A RUNX1 CD19 WASHC5 KIT HLA-DRB1 WRAP53 FLT3 CEP57 KDR TREX1 TMEM216 PDGFRA ERCC3 KIT NOTCH3 WIPF1 TERC CTLA4 NQO2 CDKN2A RSPO1 STK4 PTPN11 GJB2 KRAS MET SPINK1 PDGFRB RHOH BUB1 ND6 CDKN2C TFE3 EP300 CHIC2 HNF1B NUMA1 BRCA1 SRY FLCN MLH3 SCN10A GNPTAB KRAS NODAL TGFBR2 PPM1D DOCK8 EPAS1 PHOX2B OCA2 KCNQ1OT1 CYP2D6 ITK DICER1 PRKCD ASPSCR1 SUFU IDH1 RUNX1 ATRX FOXC2 MFN2 SAMD9L SCN4A KIF1B DHH POLE VHL POLR1D KCNAB2 BRAF SLC12A3 CARMIL2 ENPP1 NRAS LRRC8A KIT SH2B3 MST1R CEBPA NRAS MRAP TP53 ND5 FH LAMB3 CALR SLC37A4 PERP KLHDC8B FH SFTPC TGIF1 CHEK2 SLC17A9 SLC22A18 TERT CDH23 MDH2 KRT17 PTEN FGFR3 RB1 YY1 ELANE EP300 SPRTN GJB3 XPA IDH2 MAGT1 ATR GNA14 OFD1 IL7R GREM1 ESCO2 HRAS PRKAR1A MMP1 TP53 KRT17 COL14A1 RHBDF2 MPL OFD1 RYR1 IFIH1 SCN11A IDH1 JAK2 WT1 TP53 ARSA LIG4 CCBE1 FANCG KCNH1 ELANE COL18A1 HACE1 NUP214 MYC CD79A AR CDH1 BRIP1 WT1 BCR BUB1B ERCC3 KRIT1 NBN IGF2 FANCF PDGFRA BLNK PCGF2 MSH6 MEN1 FAS BRIP1 PTH1R SIX1 RNF6 BRAF DHCR7 BMPER BUB1B TP53 RET CTLA4 HABP2 ARHGAP26 DLST GCK ERCC2 RAD54L POLE HSPG2 GNA11 ADA SMAD4 BCL10 RB1 STAT1 TAF1 RPS14 BCR IL12RB1 IRF5 TMC8 TNFRSF13B CYP26C1 CALR POT1 MINPP1 POLR1C CD28 ATP7A HNF1B ERCC2 ACVR1 RPL31 VANGL1 TP63 ERCC4 SLC45A2 OFD1 LMX1B PIK3CA ASCC1 TET2 IGF2R BARD1 TUBB IGF2 BTK MSTO1 CIB1 PHB CDKN2A TNFRSF10B KIAA0753 TBX2 FOXE1 EPCAM TNFRSF13C SLC26A2 ATRX MGAT2 SKIV2L CXCR4 PIK3R1 RTEL1 TSC1 HAX1 SDHB PRKAR1A DDB2 GFI1 CDH23 XRCC3 PMVK TP53 PIK3CA GJB2 NF2 KLF6 AR ZSWIM6 SDHB CDC73 PIK3CA CCND1 GJB6 ATM SOS1 NOTCH3 DDX41 TSC2 FLT4 FGFR3 RASA1 GDF2 F5 PMS2 PTEN HBB TSC2 CASP10 ADA2 AIP WT1 LETM1 PNP COMP TRIM28 TP53 PALB2 RAD51C CCL2 CDC73 SH2D1A COX3 ZAP70 PIK3CA CYP11B2 PDGFRB PTPN11 PHOX2B FH KIT HNF4A RNASEH2C MYD88 PDE6D JAG1 TYR SEC23A FH NPM1 PHKA2 DICER1 PIK3CA HFE GNAQ DMRT3 MS4A1 MYH8 VANGL2 SHOX PUF60 GATA2 BAP1 B3GALT6 TRNS2 HRAS HDAC4 FANCG SAMHD1 GATA2 LIG4 AXIN1 TNFRSF4 OPCML PRKN FGFR2 ECM1 TGFBR2 LMNA WDPCP KCNQ1OT1 BLK GCM2 ALX1 NRAS KIT AAGAB FAH MAX RARA NEUROD1 TGFBR2 MYD88 PHF21A IDH1 MLH1 FANCB CPLX1 SMARCA4 EXTL3 AIP TERT BCL10 XIAP IGF2 SASH1 PIK3R1 PTEN NAGS TMC6 NBEAL2 NOP10 JAK2 SDHB MSH2 ECE1 BARD1 APC PMS2 CCM2 JAK2 MMEL1 RET SDHA SDHD IGHM CACNA1S FAS NR0B1 POT1 SPIB TAL2 NF2 CDON WT1 TET2 PTPRJ CD96 TRNL1 DOCK8 DCC MPL GNAQ CREBBP CDKN2A TRNK MSR1 KRT5 PRKAR1A ERBB3