SNPMiner Trials (Home Page)
Report for Mutation G12C
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 13 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 year2 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: BaselineDescription: 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: BaselineDescription: 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: BaselineDescription: 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: BaselineDescription: 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: BaselineDescription: 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: BaselineDescription: 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: BaselineDescription: 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), C1D15Description: 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, C1D15Description: 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, C1D15Description: 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, C1D15Description: 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, C1D15Description: 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, C1D15Description: 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, C1D15Description: 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, C1D15Description: 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, C1D15Description: 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, C1D15Description: 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 yearsSecondary Outcomes
Measure: Response rate in patients with a G12C mutation Time: Up to 3 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsOther 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 yearsDescription: 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 years4 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 monthsSecondary 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 month6 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 vaccineSecondary 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 12Measure: 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: - 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: - 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: - 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: - 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: - 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: - 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 monthsDescription: Blood plasma concentration
Measure: Evaluate the pharmacokinetics of MRTX849 Time: 20 monthsDescription: Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Measure: Evaluate clinical activity/efficacy of MRTX849 Time: 20 monthsSecondary Outcomes
Description: Number of participants with dose limiting toxicity
Measure: Establish maximum tolerated dose Time: 12 monthsDescription: Number of participants with dose limiting toxicity
Measure: Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents Time: 12 monthsDescription: Blood plasma concentration
Measure: Evaluate the pharmacokinetics of new MRTX849 oral formulations Time: 6 monthsDescription: Blood plasma concentration
Measure: Evaluate the pharmacokinetics of MRTX849 administered with food Time: 6 months8 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 monthsDescription: 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 monthsSecondary 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 monthsDescription: 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 monthsOther Outcomes
Description: T-cell receptor (TCR) clonality and diversity in the periphery and tumor.
Measure: T-cell receptor (TCR) Time: Up to approximately 24 months9 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 yearDescription: 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 yearsDescription: Dose tolerability
Measure: Dose interruptions, reductions and dose intensity, by treatment Time: 3 yearsSecondary Outcomes
Description: Cmax for TNO155, spartalizumab, and ribociclib
Measure: Pharmacokinetics (PK): Cmax Time: 3 yearsDescription: Tmax for TNO155, spartalizumab, and ribociclib
Measure: Pharmacokinetics (PK): Tmax Time: 3 yearsDescription: AUClast for TNO155, spartalizumab, and ribociclib
Measure: Pharmacokinetics (PK): AUClast Time: 3 yearsDescription: AUCtau for TNO155, spartalizumab, and ribociclib
Measure: Pharmacokinetics (PK): AUCtau Time: 3 yearsDescription: Overall response rate (ORR) per RECIST v1.1, by treatment
Measure: Efficacy measurements per RECIST v1.1: ORR Time: 3 yearsDescription: Disease control rate (DCR) per RECIST v1.1, by treatment
Measure: Efficacy measurements per RECIST v1.1: DCR Time: 3 yearsDescription: Progression-free survival (PFS) per RECIST v1.1, by treatment
Measure: Efficacy measurements per RECIST v1.1: PFS Time: 3 yearsDescription: Duration of response (DOR) per RECIST v1.1, by treatment
Measure: Efficacy measurements per RECIST v1.1: DOR Time: 3 yearsDescription: Overall response rate (ORR) per iRECIST for TNO155 in combination with spartalizumab
Measure: Efficacy measurements per iRECIST: ORR Time: 3 yearsDescription: Disease control rate (DCR) per iRECIST for TNO155 in combination with spartalizumab
Measure: Efficacy measurements per iRECIST: DCR Time: 3 yearsDescription: Progression-free survival (PFS) per iRECIST for TNO155 in combination with spartalizumab
Measure: Efficacy measurements per iRECIST: PFS Time: 3 yearsDescription: Duration of response (DOR) per iRECIST for TNO155 in combination with spartalizumab
Measure: Efficacy measurements per iRECIST: DOR Time: 3 yearsDescription: Overall survival (OS) by treatment
Measure: Overall Survival Time: 3 years10 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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 yearsSecondary 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 yearsDescription: 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 yearsDescription: 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 yearsDescription: 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 YearsDescription: 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 yearsDescription: 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 yearsDescription: 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 years11 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 monthsDescription: Blood plasma concentration
Measure: Evaluate the pharmacokinetics of MRTX849 and TNO155 Time: 20 monthsSecondary Outcomes
Description: Number of participants with dose limiting toxicity
Measure: Establish maximum tolerated dose Time: 12 monthsDescription: Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Measure: Evaluate clinical activity of MRTX849 Time: 20 months13 A Phase I Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-6036 in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation
This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation.
NCT04449874 Non-Small Cell Lung Cancer Colorectal Cancer Advanced Solid Tumors Drug: GDC-6036 MeSH:Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms
HPO:Neoplasm of the large intestine Non-small cell lung carcinoma
A Phase I Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-6036 in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation. --- G12C ---
A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation. --- G12C ---
A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation. --- G12C --- --- G12C ---
Inclusion Criteria: - Histologically documented advanced or metastatic solid tumor with KRAS G12C mutation. --- G12C ---
Exclusion Criteria: - Active brain metastases - Malabsorption or other condition that interferes with enteral absorption - Clinically significant cardiovascular dysfunction or liver disease Inclusion Criteria: - Histologically documented advanced or metastatic solid tumor with KRAS G12C mutation. --- G12C ---
Primary Outcomes
Measure: Percentage of Participants With Adverse Events (AEs) Time: From baseline up until 28 days after the final doseMeasure: Percentage of Participants With Dose-Limiting Toxicities (DLTs) Time: Days 1-21 of Cycle 1 (a cycle is 21 days)
Measure: Percentage of Participants With Changes From Baseline in Targeted Vital Signs Time: From baseline up until 28 days after the final dose
Measure: Percentage of Participants With Changes From Baseline in Targeted Clinical Laboratory Test Results Time: From baseline up until 28 days after the final dose
Measure: Percentage of Participants With Changes From Baseline in Targeted ECG Parameters Time: From baseline up until 28 days after the final dose
Secondary Outcomes
Measure: Plasma Concentration of GDC-6036 Time: From baseline up until 28 days after the final dose or at study treatment discontinuation visitMeasure: Objective Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) Time: Up to 42 months
Measure: Duration of Response (DOR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) Time: Up to 42 months
Measure: Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) Time: Up to 42 months