SNPMiner Trials by Shray Alag


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Report for Mutation G12C

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 12 clinical trials

Clinical Trials


1 Pilot Study Of Safety And Feasibility Of GI-4000, An Inactivated Recombinant Saccharomyces Cerevisiae Expressing Mutant Ras Protein Combined With Adoptive Transfer And Chemoradiation in Locally Advanced Pancreatic Cancer

The purpose of this study is to determine if it is safe to add multiple immunotherapies to standard chemotherapy and radiation for treating pancreatic cancer tumors that cannot be completely removed by surgery. 1. GI-4000 Vaccination: The first involves a "vaccine," which is an injection (shot) that teaches your immune system to attack foreign invaders. The vaccine we will use is called "GI-4000" - a vaccine composed of yeast that is made to carry the same proteins (called "mutated Ras proteins") found in some pancreatic cancer cells. 2. Adoptive T-cell Transfer: The second type of immunotherapy in this study is called "adoptive T-cell transfer." This involves collecting a specific type of white blood cells from you (called "T-cells")and growing T-cells grown in a lab which may help the research participants' immune systems recover more quickly after chemotherapy, and possibly improved response to other immunotherapies. We hope that studying these agents together will teach us how to help the immune system fight pancreatic cancer.

NCT00837135 Pancreatic Cancer Other: Screening Biological: GI-4000 Vaccine Biological: GI-4000 Vaccine + Activated T Cells Biological: Surgical Evaluation after Vaccine #4
MeSH:Pancreatic Neoplasms
HPO:Neoplasm of the pancreas

1. Histologically-confirmed pancreatic adenocarcinoma that expresses one of the GI-4000-related k-ras oncoproteins (G12V, G12C, G12D, Q61L, or Q61R) 2. Locally advanced disease, (stages I-III, i.e no evidence of metastasis outside the pancreas and its regional lymph nodes). --- G12V --- --- G12C ---

Primary Outcomes

Measure: To evaluate the feasibility of incorporating GI-4000 vaccine and activated T-cell infusion into a regimen of chemotherapy, radiation, and surgical resection to treat locally advanced pancreatic cancer.

Time: 1 year

2 A Phase 1, Open-label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of Combined Oral C-met/Alk Inhibitor (Pf-02341066) And Pan-her Inhibitor (Pf-00299804) In Patients With Advanced Non-small Cell Lung Cancer

Lung cancer tumors become resistant to the first generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib by changing and increasing the activity of two cell signaling pathways: the cMET pathway and the EGFR pathway. Both resistance mechanisms can occur at the same time, in the same patient and even in the same tumor. This study combines a second generation EGFR inhibitor and a cMET inhibitor to block both these pathways in order to overcome resistance and treat this disease.

NCT01121575 Non Small Cell Lung Cancer Drug: PF-02341066 Drug: PF-00299804 Drug: PF-02341066 Drug: PF-00299804
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

Sample analyses were performed in accordance to Good Laboratory Practice (GLP) guidance and included mutation detection for EGFR gene.. Number of Participants With KRAS Mutation (GLY12CYS) at Baseline. --- GLY12CYS ---

Primary Outcomes

Description: AE was any untoward medical occurrence with study drug/ device in a trial participant. Serious adverse event (SAE) was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

Measure: Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase

Time: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

Description: AE was any untoward medical occurrence with study drug/ device in a trial participant. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

Measure: Overview of Treatment-emergent All Causalities AEs in Expansion Phase

Time: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

Description: An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

Measure: Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase

Time: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

Description: An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

Measure: Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase

Time: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

Description: DLTs were those AEs which occurred in Cycle 1 of treatment in Dose Escalation Phase which may be attributed to study drug [combined Crizotinib (PF-02341066) plus Dacomitinib (PF-00299804)] without a clear alternative explanation and despite the use of adequate/maximal medical intervention as dictated by local institutional clinical practices or the judgment of the investigator. The following events were considered DLTs (using CTCAE version 4.02);1. Grade ≥4 hematologic events. 2. Grade ≥3 non-hematological events (except Grade 3/4 asymptomatic hypophosphatemia and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea had to have persisted at Grade 3 or 4 despite maximal medical therapy. Grade 3 hypertension will be considered a DLT only if the event is unmanageable by standard approved pharmacologic agents or if the symptomatic sequelae are identified despite appropriate medical intervention.

Measure: Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase

Time: Cycle 1 (4 weeks)

Secondary Outcomes

Description: If a participant had not achieved an objective response with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) - 1.1 as determined by the investigators, relative to the response evaluable population, but remained stable for at least 6 weeks after first dose, then the best overall response for such a participant was considered as stable disease.

Measure: Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase

Time: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Description: If a participant had not achieved an objective response with confirmed complete response (CR) or partial response (PR) according to RECIST (1.1) as determined by the investigators, relative to the response evaluable population, but remained stable for at least 6 weeks after first dose, then the best overall response for such a participant was considered as stable disease.

Measure: Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase

Time: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Description: ORR was defined as the percent of participants with CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) determined by study physicians, relative to the response evaluable population. Participants were considered non-responders until proven otherwise. Thus, participants who: 1) Did not have CR or PR while on study, or 2) Did not have a post-baseline tumor evaluation, or 3) Received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or 4) Died, in progress, or drop out for any reason prior to reaching a CR or PR, were counted as non-responders in the assessment of ORR. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors were confirmed by repeated tumor assessment that were performed 4 weeks after the criteria for response were first met.

Measure: Number of Participants With Objective Response Rate (ORR) in Escalation Phase

Time: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Description: ORR was defined as the percent of participants with CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) determined by study physicians, relative to the response evaluable population. Participants were considered non-responders until proven otherwise. Thus, participants who: 1) Did not have CR or PR while on study, or 2) Did not have a post-baseline tumor evaluation, or 3) Received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or 4) Died, in progress, or drop out for any reason prior to reaching a CR or PR, were counted as non-responders in the assessment of ORR. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors were confirmed by repeated tumor assessment that were performed 4 weeks after the criteria for response were first met.

Measure: Number of Participants With ORR in Expansion Phase

Time: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Description: This outcome measure presented the duration of response for one participant in expansion cohort 1 who showed partial response.

Measure: Duration of Response for the Only Participant Shown Partial Response in Expansion Phase

Time: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Description: PFS was defined as the time from the date of the first dose to the date of the first documentation of objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used.

Measure: Progression Free Survival (PFS) in Escalation Phase

Time: From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Description: PFS was defined as the time from the date of the first dose to the date of the first documentation of objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used.

Measure: Progression Free Survival (PFS) in Expansion Phase

Time: From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Description: Tumor biomarkers such as HGF, EGFR, and c-Met were analyzed in tumor cells (neoplastic compartment) of tumor specimens from both expansion cohorts 1 and 2 by IHC. The H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+, where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum calculated score of 0 to maximum calculated score of 300, where 0 correspond to no expression and maximum score of 300 indicates the strongest expression. However, the biomarker expression level (higher or lower) was not a predictor of outcome.

Measure: Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method

Time: Baseline

Description: Expression of tumor biomarkers EGFR and cMet at Baseline (using FISH method) are presented in this outcome measure.

Measure: Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method

Time: Baseline

Description: Participants showed amplification of c-Met, HER2, and EGFR in the tumor cells and gene rearrangement of ALK are presented in this outcome measure.

Measure: Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method

Time: Baseline

Description: This outcome measure presented the plasma concentration of sMet at different study visits. s-Met was analyzed using an enzyme-linked immunosorbent assay (ELISA).

Measure: Plasma Concentration of sMet by Study Visits

Time: At screening and Cycle 1 Day 1 (C1D1) (6 hours post dose), and C1D15, C2D1, C2D15 (all predose).

Description: Sample analyses were performed in accordance to Good Laboratory Practice (GLP) guidance and included mutation detection for EGFR gene.

Measure: Number of Participants With EGFR Mutation at Baseline

Time: Baseline

Description: Sample analyses were performed in accordance to GLP guidance and included mutation detection for KRAS gene.

Measure: Number of Participants With KRAS Mutation (GLY12CYS) at Baseline

Time: Baseline

Description: Sample analyses were performed in accordance to GLP guidance and included mutation detection for PIK3CA gene.

Measure: Number of Participants With PIK3CA Mutation at Baseline

Time: Baseline

Description: Sample analyses were performed in accordance to GLP guidance and included translocation detection (RNA based) for ROS1 gene.

Measure: Number of Participants With ROS1 Gene Translocation at Baseline

Time: Baseline

Description: At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUClast for crizotinib and PF-06260182. AUClast was calculated using Linear/Log trapezoidal method.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Concentration (AUClast)

Time: Cycle 1 (C1)/Day 1 (D1), C1D15

Description: At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). AUC10 was calculated using Linear/Log trapezoidal method. The below analysis table included geometric Mean and Geometric Coefficient of Variation of AUC10 for crizotinib and PF-06260182. Arithmetic mean was presented if the n=2.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10)

Time: C1D1, C1D15

Description: At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Cmax for crizotinib and PF-06260182. Cmax was observed directly from data.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax)

Time: C1D1, C1D15

Description: At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tlast for crizotinib and PF-06260182. Tlast was observed directly from data.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast)

Time: C1D1, C1D15

Description: At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tmax for crizotinib and PF-06260182. Tmax was observed directly from data as time of first occurrence.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax)

Time: C1D1, C1D15

Description: At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUClast for dacomitinib and PF-05199265. AUClast was calculated using Linear/Log trapezoidal method.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast

Time: C1D1, C1D15

Description: At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUC24 for dacomitinib and PF-05199265. AUC24 was calculated using Linear/Log trapezoidal method.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24

Time: C1D1, C1D15

Description: At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Cmax for dacomitinib and PF-05199265. Cmax was observed directly from data.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax

Time: C1D1, C1D15

Description: At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tlast for dacomitinib and PF-05199265. Tlast was observed directly from data.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast

Time: C1D1, C1D15

Description: At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tmax for dacomitinib and PF-05199265. Tmax was observed directly from data as time of first occurrence.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax

Time: C1D1, C1D15

Description: Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for AUClast. AUClast was calculated using Linear/Log trapezoidal method.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUClast

Time: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Description: Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for AUC10. AUC10 was calculated using Linear/Log trapezoidal method.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUC10

Time: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Description: Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Cmin. Cmin was observed directly from data.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmin

Time: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Description: Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Cmax. Cmax was observed directly from data.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmax

Time: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Description: Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Tlast. Tlast was observed directly from data.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tlast

Time: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Description: Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Tmax. Tmax was observed directly from data as time of first occurrence.

Measure: Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tmax

Time: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Description: PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (AUClast) following dacomitinib alone and in combination with crizotinib are summarized in the below table. AUClast was calculated using Linear/Log trapezoidal method.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUClast

Time: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)

Description: PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (AUC24) following dacomitinib alone and in combination with crizotinib are summarized in the below table. AUC24 was calculated using Linear/Log trapezoidal method.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUC24

Time: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)

Description: PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Cmin) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Cmin was observed directly from data.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmin

Time: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)

Description: PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Cmax) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Cmax was observed directly from data.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmax

Time: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)

Description: PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Tlast) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Tlast was observed directly from data.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tlast

Time: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)

Description: PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Tmax) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Tmax was observed directly from data as time of first occurrence.

Measure: Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tmax

Time: Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)

3 A Phase II Trial of Trametinib With Docetaxel in Patients With KRAS Mutation Positive Non-Small Cell Lung Cancer (NSCLC) and Progressive Disease Following One or Two Prior Systemic Therapies

This phase II trial studies how well trametinib and docetaxel work in treating patients with stage IV KRAS mutation positive non-small cell lung cancer or cancer that has come back. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trametinib with docetaxel may work better in treating non-small cell lung cancer.

NCT02642042 KRAS Gene Mutation Recurrent Lung Non-Small Cell Carcinoma Stage IV Lung Non-Small Cell Cancer AJCC v7 Drug: Docetaxel Other: Laboratory Biomarker Analysis Drug: Trametinib
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

Response rate (confirmed and unconfirmed complete and partial responses) in all KRAS mutant patients (both those with G12C mutations and those with non-G12C mutations). --- G12C ---

Response rate (confirmed and unconfirmed complete and partial responses) in all KRAS mutant patients (both those with G12C mutations and those with non-G12C mutations). --- G12C --- --- G12C ---

Response rate in patients with a G12C mutation. --- G12C ---

SECONDARY OBJECTIVES: I. To evaluate if trametinib plus docetaxel is consistent with promise of activity measured by the response rate in G12C KRAS mutation positive NSCLC patients following one or two prior systemic therapies. --- G12C ---

To assess the response rate of this combination in non-G12C KRAS mutation positive NSCLC patients. --- G12C ---

To assess progression-free survival within the G12C and non-G12C KRAS positive subgroups and the entire study population. --- G12C ---

To assess progression-free survival within the G12C and non-G12C KRAS positive subgroups and the entire study population. --- G12C --- --- G12C ---

V. To assess overall survival within G12C positive patients, non-G12C positive patients, and the entire study population. --- G12C ---

V. To assess overall survival within G12C positive patients, non-G12C positive patients, and the entire study population. --- G12C --- --- G12C ---

Primary Outcomes

Measure: Response rate (confirmed and unconfirmed complete and partial responses) in all KRAS mutant patients (both those with G12C mutations and those with non-G12C mutations)

Time: Up to 3 years

Secondary Outcomes

Measure: Response rate in patients with a G12C mutation

Time: Up to 3 years

Description: Progression free survival estimates will be calculated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.

Measure: Progression free survival

Time: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Description: Overall survival estimates will be calculated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.

Measure: Overall survival

Time: Up to 3 years

Description: Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (CTCAE version 5.0 will be utilized for serious adverse event reporting only). Toxicity rates can be estimated to within +/- 14% with 95% confidence.

Measure: Incidence of toxicity

Time: Up to 3 years

Other Outcomes

Description: The response rate between patients with dysfunctional p53 will be compared to the response rate in patients without p53 dysfunction.

Measure: Response rates in the presence of p53 mutations

Time: Up to 3 years

Description: The response rate between patients with LKB1 disruption will be compared to the response rate in patients without LKB1 disruption. The response rate will be estimated by LKB1 disruption status (yes/no), along with 95% confidence intervals around the estimated proportions. This analysis will evaluate if disruption in LKB1 is associated with a lower probability of response.

Measure: Response rates in the presence of LKB1 mutations

Time: Up to 3 years

4 Chemotherapy in KRAS Mutated Chemotherapy Naive Non-small Cell Lung Cancer Patients: a Phase III Study Comparing Cisplatin-pemetrexed With Carboplatin-paclitaxel-bevacizumab: NVALT 22

The purpose of this study is to determine whether carboplatin-paclitaxel-bevacizumab results in a prolonged progression free survival compared to cisplatin-pemetrexed as first line treatment in patients with KRAS mutated non-small cell lung cancer.

NCT02743923 Carcinoma, Non-Small Cell Lung Drug: carboplatin Drug: paclitaxel Drug: Bevacizumab Drug: Pemetrexed Drug: cisplatin
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

Stratification for KRAS mutation (G12V versus G12C versus other). --- G12V --- --- G12C ---

outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets).. --- G12V --- --- G12C ---

The two most common KRAS types are G12C in about 40% of cases, G12V in 18% and G12D in 15% of cases. --- G12C ---

Stratification for KRAS mutation (G12V versus G12C versus other) at randomization.. response by Crabb criteria (if applicable). --- G12V --- --- G12C ---

Primary Outcomes

Measure: progression free survival

Time: Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months

Secondary Outcomes

Measure: disease control rate

Time: Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months.

Description: Stratification for KRAS mutation (G12V versus G12C versus other)

Measure: overall survival

Time: date of randomization to the date of death from any cause, assessed up to 60 months.

Description: The two most common KRAS types are G12C in about 40% of cases, G12V in 18% and G12D in 15% of cases. Subgroup analyses are planned to explore treatment effect in these different KRAS mutations groups. At baseline the metastatic patterns of these subgroups will be described. KRAS mutations in NSCLC occur mainly in codon 12 and 13. Stratification for KRAS mutation (G12V versus G12C versus other) at randomization.

Measure: outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets).

Time: date of randomization to the date of death from any cause, assessed up to 60 months.

Measure: response by Crabb criteria (if applicable)

Time: Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months

5 Comparison of KRAS/BRAF Mutational Status Between Tumor Tissue Section Analysis With Conventional Techniques and Plasma Samples Analysis (KPLEX2)

The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients.

NCT02784639 Colorectal Cancer Other: Plasma Analysis of circulating cell free DNA Other: Tumor tissue analysis of circulating cell free DNA
MeSH:Colorectal Neoplasms
HPO:Neoplasm of the large intestine

As a consequence, the method was adapted to detect the six more frequent KRAS mutations in CRC (G12D, G12V, G13D, G12S, G12C, G12A) and the BRAF V600E. --- G12D --- --- G12V --- --- G13D --- --- G12S --- --- G12C ---

Primary Outcomes

Description: Area under the ROC curve of the mutation percentage obtained from plasma ccfDNA analysis

Measure: Area under ROC curve

Time: 12 month

6 Pilot Study of Mature Dendritic Cell Vaccination Against Mutated KRAS in Patients With Resectable Pancreatic Cancer

This research study is designed to evaluate the effects of a dendritic cell (kind of white blood cell) vaccine for pancreatic cancer.

NCT03592888 Pancreatic Ductal Adenocarcinoma Drug: mDC3/8-KRAS Vaccine
MeSH:Adenocarcinoma

Inclusion Criteria: - Pathologically-confirmed KRAS(G12D-), KRAS(G12V-), KRAS(G12R-) or KRAS(G12C-mutated) pancreatic ductal adenocarcinoma who are at high risk of relapse and have no evidence of disease. --- G12D --- --- G12V --- --- G12R --- --- G12C ---

Primary Outcomes

Measure: Safety and side effects of vaccine per CTCAE 4.0

Time: At time of consent through 30 days after the subject's last DC vaccine

Secondary Outcomes

Measure: Immune response measuring increased numbers of peptide specific T cells as calculated by the peptide-MHC multimer assay.

Time: Day 1 through week 12

Measure: Disease Free Survival

Time: 30 days following second vaccine through study completion approximately 12 months after the first DC vaccine

7 A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in patients with advanced solid tumors that have a KRAS G12C mutation.

NCT03785249 Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Drug: MRTX849 Drug: Pembrolizumab Drug: Cetuximab Drug: Afatinib
MeSH:Neoplasm Metastasis Neoplasms
HPO:Neoplasm

A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1. --- G12C ---

Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1 This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C ---

Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1 This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C --- --- G12C ---

Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation. --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - Active brain metastases - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - Active brain metastases - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - Active brain metastases - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - Active brain metastases - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - Active brain metastases - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation - Unresectable or metastatic disease - Standard treatment is not available or patient declines - Adequate organ function Exclusion Criteria: - Active brain metastases - History of intestinal disease or major gastric surgery or inability to swallow oral medications - Other active cancer Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C --- --- G12C ---

MRTX849 is an orally-available small molecule inhibitor of KRAS G12C. --- G12C ---

Primary Outcomes

Description: Number of participants with treatment related adverse events

Measure: Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation

Time: 20 months

Description: Blood plasma concentration

Measure: Evaluate the pharmacokinetics of MRTX849

Time: 20 months

Description: Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Measure: Evaluate clinical activity/efficacy of MRTX849

Time: 20 months

Secondary Outcomes

Description: Number of participants with dose limiting toxicity

Measure: Establish maximum tolerated dose

Time: 12 months

Description: Number of participants with dose limiting toxicity

Measure: Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents

Time: 12 months

Description: Blood plasma concentration

Measure: Evaluate the pharmacokinetics of new MRTX849 oral formulations

Time: 6 months

Description: Blood plasma concentration

Measure: Evaluate the pharmacokinetics of MRTX849 administered with food

Time: 6 months

8 A Phase 1, Open-Label, Multicenter Study to Assess the Safety and Tolerability of mRNA-5671/V941 as a Monotherapy and in Combination With Pembrolizumab in Participants With KRAS Mutant Advanced or Metastatic Non-Small Cell Lung Cancer, Colorectal Cancer or Pancreatic Adenocarcinoma

This study will determine the safety and tolerability and establish a preliminary recommended Phase 2 dose of V941(mRNA-5671/V941) as a monotherapy and in combination with pembrolizumab infusion.

NCT03948763 Neoplasms Carcinoma, Non-Small-Cell Lung Pancreatic Neoplasms Colorectal Neoplasms Biological: V941 Biological: Pembrolizumab
MeSH:Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Pancreatic Neoplasms Neoplasms
HPO:Neoplasm Neoplasm of the large intestine Neoplasm of the pancreas Non-small cell lung carcinoma

All - Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor identified by local laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit. --- G12D --- --- G12V --- --- G13D --- --- G12C ---

Primary Outcomes

Description: The following toxicities graded for severity using NCI Common Terminology for Adverse Events (CTCAE), Version 4.0 will be considered a DLT if judged by the investigator to be possibly related to study investigational products: 1) Grade 4 nonhematologic toxicity (ie. not a laboratory finding). 2) Grade 4 hematologic toxicity lasting ≥ 7 days, except thrombocytopenia: 3) Grade 4 thrombocytopenia of any duration 4) Grade 3 thrombocytopenia associated with clinically significant bleeding 5) Any nonhematologic AE ≥ Grade 3 in severity, with some exceptions 6) Any Grade 3 or Grade 4 nonhematologic laboratory value that meets one of the study criteria 7) Febrile neutropenia Grade 3 or Grade 4 8) Prolonged delay (> 2 weeks) in initiating Cycle 2 due to treatment-related toxicity. 9) Any treatment-related toxicity that causes the participant to discontinue treatment during Cycle 1. 10) Grade 5 toxicity 11) Any other clinically significant toxicity judged to be a DLT by the investigator.

Measure: Dose-Limiting Toxicities (DLTs)

Time: Cycle 1 (Up to 21 days)

Description: Number of participants who experienced an AE. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Measure: Adverse Events (AEs)

Time: Up to approximately 25 months

Description: Number of participants who discontinued from study due to an AE. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Measure: Discontinuations

Time: Up to approximately 24 months

Secondary Outcomes

Description: ORR is assessed by the investigator based on Response Rate Assessed by Modified Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and RECIST for immune-based therapeutics (iRECIST) following administration of V941 in combination with pembrolizumab. Objective response is a confirmed complete response (CR) or partial response (PR).

Measure: Objective Response Rate (ORR)

Time: Up to approximately 24 months

Description: Presence of and changes in the quantity of mutant KRAS specific T cells in the blood.

Measure: Mutant KRAS Specific T cells

Time: Up to approximately 24 months

Other Outcomes

Description: T-cell receptor (TCR) clonality and diversity in the periphery and tumor.

Measure: T-cell receptor (TCR)

Time: Up to approximately 24 months

9 A Phase Ib, Open-label, Multi-center Study to Characterize the Safety, Tolerability, and Preliminary Efficacy of TNO155 in Combination With Spartalizumab or Ribociclib in Selected Malignancies

This study is a Phase Ib, multi-center, open-label study of TNO155 in combination with spartalizumab or ribociclib with a dose escalation part followed by a dose expansion part in adult subjects with advanced solid tumors. These two treatment arms will enroll subjects in parallel to characterize the safety, tolerability, PK, PD and preliminary antitumor activity. The study treatment will be administered until the subject experiences unacceptable toxicity, progressive disease, and/or has treatment discontinued at the discretion of the Investigator or the subject, or due to withdrawal of consent.

NCT04000529 Non-small Cell Lung Carcinoma Head and Neck Squamous Cell Carcinoma Esophageal SCC Gastrointestinal Stromal Tumors Colorectal Cancer Drug: TNO155 Drug: Spartalizumab Drug: Ribociclib
MeSH:Carcinoma Squamous Cell Carcinoma of Head and Neck Gastrointestinal Stromal Tumors Carcinoma, Non-Small-Cell Lung Esophageal Squamous Cell Carcinoma
HPO:Carcinoma Gastrointestinal stroma tumor Non-small cell lung carcinoma

For TNO155 plus spartalizumab combination: i. Advanced EGFR WT, ALK WT, KRAS G12C NSCLC after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy. --- G12C ---

Primary Outcomes

Description: Incidence of dose limiting toxicities (DLTs) during the first cycle of combination treatment during the dose escalation part

Measure: DLT incidence

Time: 1 year

Description: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment

Measure: AE and SAE incidence

Time: 3 years

Description: Dose tolerability

Measure: Dose interruptions, reductions and dose intensity, by treatment

Time: 3 years

Secondary Outcomes

Description: Cmax for TNO155, spartalizumab, and ribociclib

Measure: Pharmacokinetics (PK): Cmax

Time: 3 years

Description: Tmax for TNO155, spartalizumab, and ribociclib

Measure: Pharmacokinetics (PK): Tmax

Time: 3 years

Description: AUClast for TNO155, spartalizumab, and ribociclib

Measure: Pharmacokinetics (PK): AUClast

Time: 3 years

Description: AUCtau for TNO155, spartalizumab, and ribociclib

Measure: Pharmacokinetics (PK): AUCtau

Time: 3 years

Description: Overall response rate (ORR) per RECIST v1.1, by treatment

Measure: Efficacy measurements per RECIST v1.1: ORR

Time: 3 years

Description: Disease control rate (DCR) per RECIST v1.1, by treatment

Measure: Efficacy measurements per RECIST v1.1: DCR

Time: 3 years

Description: Progression-free survival (PFS) per RECIST v1.1, by treatment

Measure: Efficacy measurements per RECIST v1.1: PFS

Time: 3 years

Description: Duration of response (DOR) per RECIST v1.1, by treatment

Measure: Efficacy measurements per RECIST v1.1: DOR

Time: 3 years

Description: Overall response rate (ORR) per iRECIST for TNO155 in combination with spartalizumab

Measure: Efficacy measurements per iRECIST: ORR

Time: 3 years

Description: Disease control rate (DCR) per iRECIST for TNO155 in combination with spartalizumab

Measure: Efficacy measurements per iRECIST: DCR

Time: 3 years

Description: Progression-free survival (PFS) per iRECIST for TNO155 in combination with spartalizumab

Measure: Efficacy measurements per iRECIST: PFS

Time: 3 years

Description: Duration of response (DOR) per iRECIST for TNO155 in combination with spartalizumab

Measure: Efficacy measurements per iRECIST: DOR

Time: 3 years

Description: Overall survival (OS) by treatment

Measure: Overall Survival

Time: 3 years

10 A First-in-Human Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of JNJ-74699157 in Participants With Advanced Solid Tumors Harboring the KRAS G12C Mutation

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion).

NCT04006301 Neoplasms Advanced Solid Tumors Non-small Cell Lung Cancer Colorectal Cancer Drug: JNJ-74699157
MeSH:Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms
HPO:Neoplasm of the large intestine Non-small cell lung carcinoma

A First-in-Human Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of JNJ-74699157 in Participants With Advanced Solid Tumors Harboring the KRAS G12C Mutation. --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C --- --- G12C ---

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion). --- G12C --- --- G12C --- --- G12C ---

AUC (0-last) is the area under the plasma concentration-time curve from time zero to last observed quantifiable concentration.. Part 1 and 2: Percentage of KRAS G12C Protein in Tumor Tissue Covalently Bound with JNJ-74699157 or its Metabolites. --- G12C ---

Percentage of kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) protein in tumor tissue covalently bound with JNJ-74699157 or its metabolites will be evaluated using mass spectroscopy.. Part 1: Overall Response Rate. --- G12C ---

Change from baseline in QTcF intervals will be assessed.. Inclusion Criteria: - Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation in tumor tissue or blood - Histological documentation of disease: Part 1: Histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable, Part 2: (a) unresectable, locally advanced (Stage IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), (b) Solid tumor malignancy other than NSCLC that is metastatic or unresectable - Received or was ineligible for standard treatment options. --- G12C ---

Participants who have had complete surgical resection of or received stereotactic radiosurgery to less than or equal to (<=) 3 metastatic lesions will be permitted to enroll in the study within 14 days of such treatment if they have recovered from treatment, are clinically stable, and do not require prolonged systemic corticosteroid therapy as noted above - Prior treatment with an inhibitor specific to KRAS G12C - Prior solid organ transplantation - History of malignancy (other than the disease under study) within 2 years before the first administration of study drug. --- G12C ---

If any of these conditions exist, the investigator should discuss with the sponsor to determine participant eligibility Inclusion Criteria: - Kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation in tumor tissue or blood - Histological documentation of disease: Part 1: Histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable, Part 2: (a) unresectable, locally advanced (Stage IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC), (b) Solid tumor malignancy other than NSCLC that is metastatic or unresectable - Received or was ineligible for standard treatment options. --- G12C ---

This study will evaluate JNJ-74699157, a potent and specific, orally bioavailable inhibitor of the glycine-to-cysteine (G12C) mutant KRAS protein, which is found in non-small cell lung cancers and other solid tumor types. --- G12C ---

This study will enroll participants with advanced solid tumors harboring the KRAS G12C mutation and will be conducted in 2 parts. --- G12C ---

Primary Outcomes

Description: DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

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

Time: Up to 2 years

Description: An AE is any untoward medical occurrence in a participant who received study drug without regard to causal relationship.

Measure: Part 1 and Part 2: Number of Participants with Adverse Events (AEs)

Time: Up to 4 years

Description: Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life threatening consequences; Grade 5: Death.

Measure: Part 1 and Part 2: Number of Participants with AE's by Severity

Time: Up to 4 years

Description: ORR is defined as the percentage of participants who have a partial response (PR) or better response as per RECIST v.1.1. PR criteria in solid tumors (RECIST) is greater than or equal to (>=) 30 percent (%) decrease in the sum of the diameters of all index lesions compared with baseline in 2 observations at least 4 weeks apart, in absence of new lesions or unequivocal progression of non-index lesions.

Measure: Part 2: Overall Response Rate (ORR)

Time: Up to 4 years

Secondary Outcomes

Description: Cmax is the maximum observed plasma concentration.

Measure: Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-74699157

Time: Up to 4 years

Description: Tmax is defined as actual sampling time to reach maximum observed plasma concentration.

Measure: Part 1 and Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-74699157

Time: Up to 4 years

Description: AUC (0-last) is the area under the plasma concentration-time curve from time zero to last observed quantifiable concentration.

Measure: Part 1 and 2: Area Under Plasma-concentration Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-last])

Time: Up to 4 years

Description: Percentage of kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) protein in tumor tissue covalently bound with JNJ-74699157 or its metabolites will be evaluated using mass spectroscopy.

Measure: Part 1 and 2: Percentage of KRAS G12C Protein in Tumor Tissue Covalently Bound with JNJ-74699157 or its Metabolites

Time: Up to 4 Years

Description: ORR is defined as the percentage of participants who have a PR or better response as per RECIST v.1.1. PR criteria in solid tumors (RECIST) is >=30 percent % decrease in the sum of the diameters of all index lesions compared with baseline in 2 observations at least 4 weeks apart, in absence of new lesions or unequivocal progression of non-index lesions.

Measure: Part 1: Overall Response Rate

Time: Up to 4 years

Description: DOR is defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease (PD), as defined in the RECIST v1.1, or death due to any cause, whichever occurs first. PD is assessed if the sum of the diameters has increased by >=20% and >=5 millimeter (mm) from nadir (including baseline if it is the smallest sum).

Measure: Part 1 and Part 2: Duration of Response (DOR)

Time: Up to 4 years

Description: Change from baseline in QTcF intervals will be assessed.

Measure: Change From Baseline in QTc Interval Based on the Fridericia Correction (QTcF) Method

Time: Baseline up to 4 years

11 A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation

The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation.

NCT04165031 Advanced Solid Tumor Non-Small Cell Lung Cancer Colorectal Cancer Drug: LY3499446 Drug: Abemaciclib Drug: Cetuximab Drug: Erlotinib Drug: Docetaxel
MeSH:Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms
HPO:Neoplasm of the large intestine Non-small cell lung carcinoma

A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation. --- G12C ---

A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation. --- G12C ---

A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation. --- G12C --- --- G12C ---

Inclusion Criteria: - Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body - For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health - Participants must be willing to use highly effective birth control - Participants must have adequate organ function - Participants must be able to swallow capsules Exclusion Criteria: - Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled - Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months - Participants must not have cancer of the central nervous system that is not stable - Participants must not be pregnant or breastfeeding - Participants must not use herbal supplements Inclusion Criteria: - Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body - For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health - Participants must be willing to use highly effective birth control - Participants must have adequate organ function - Participants must be able to swallow capsules Exclusion Criteria: - Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled - Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months - Participants must not have cancer of the central nervous system that is not stable - Participants must not be pregnant or breastfeeding - Participants must not use herbal supplements Advanced Solid Tumor Non-Small Cell Lung Cancer Colorectal Cancer Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms null --- G12C ---

Inclusion Criteria: - Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body - For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health - Participants must be willing to use highly effective birth control - Participants must have adequate organ function - Participants must be able to swallow capsules Exclusion Criteria: - Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled - Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months - Participants must not have cancer of the central nervous system that is not stable - Participants must not be pregnant or breastfeeding - Participants must not use herbal supplements Inclusion Criteria: - Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body - For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health - Participants must be willing to use highly effective birth control - Participants must have adequate organ function - Participants must be able to swallow capsules Exclusion Criteria: - Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled - Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months - Participants must not have cancer of the central nervous system that is not stable - Participants must not be pregnant or breastfeeding - Participants must not use herbal supplements Advanced Solid Tumor Non-Small Cell Lung Cancer Colorectal Cancer Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms null --- G12C --- --- G12C ---

Primary Outcomes

Description: Phase 1: Number or Participants with DLTs

Measure: Phase 1: Number or Participants with Dose Limiting Toxicities (DLTs)

Time: Cycle 1 (21 Day Cycle)

Description: Phase 2: ORR: Percentage of Participants Who Achieve CR or PR (CRC Cohorts and Other Tumors Cohort)

Measure: Phase 2: Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) (CRC Cohorts and Other Tumors Cohort)

Time: Baseline through Measured Progressive Disease (Estimated up to 24 Months)

Description: Phase 2: PFS (NSCLC Cohorts)

Measure: Phase 2: Progression-Free Survival (PFS) (NSCLC Cohorts)

Time: Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 24 Months)

Secondary Outcomes

Description: PK: Average Concentration at Steady State of LY3499446

Measure: Pharmacokinetics (PK): Average Concentration at Steady State of LY3499446

Time: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)

Description: PK: Average Concentration at Steady State of LY3499446 in Combination with Abemaciclib

Measure: PK: Average Concentration at Steady State of LY3499446 in Combination with Abemaciclib

Time: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)

Description: PK: Average Concentration at Steady State of LY3499446 in Combination with Cetuximab

Measure: PK: Average Concentration at Steady State of LY3499446 in Combination with Cetuximab

Time: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)

Description: PK: Average Concentration at Steady State of LY3499446 in Combination with Erlotinib

Measure: PK: Average Concentration at Steady State of LY3499446 in Combination with Erlotinib

Time: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)

Description: Phase 1: ORR: Percentage of Participants Who Achieve CR or PR

Measure: Phase 1: ORR: Percentage of Participants Who Achieve CR or PR

Time: Baseline through Measured Progressive Disease (Estimated up to 24 Months)

Description: Phase 1: PFS

Measure: Phase 1: PFS

Time: Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 24 Months)

Description: DoR

Measure: Duration of Response (DoR)

Time: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated up to 24 Months)

Description: Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, and SD

Measure: Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, and SD

Time: Baseline through Measured Progressive Disease (Estimated up to 24 Months)

12 A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.

NCT04330664 Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Drug: MRTX849 Drug: TNO155
MeSH:Neoplasm Metastasis Neoplasms
HPO:Neoplasm

A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation. --- G12C ---

Phase 1/2 Study in Patients With Cancer Having a KRAS G12C Mutation This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C ---

Phase 1/2 Study in Patients With Cancer Having a KRAS G12C Mutation This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation. --- G12C --- --- G12C ---

Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.. Number of participants with treatment related adverse events. --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C ---

Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Inclusion Criteria: - Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer) - Unresectable or metastatic disease - No available treatment with curative intent - Adequate organ function Exclusion Criteria: - History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow - Other active cancer - Cardiac abnormalities Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Neoplasm Metastasis Neoplasms This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C --- --- G12C ---

MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2. --- G12C ---

Primary Outcomes

Description: Number of participants with treatment related adverse events

Measure: Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation.

Time: 20 months

Description: Blood plasma concentration

Measure: Evaluate the pharmacokinetics of MRTX849 and TNO155

Time: 20 months

Secondary Outcomes

Description: Number of participants with dose limiting toxicity

Measure: Establish maximum tolerated dose

Time: 12 months

Description: Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Measure: Evaluate clinical activity of MRTX849

Time: 20 months


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