A Phase 1b, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Sotorasib Monotherapy and in Combination With Other Anti-cancer Therapies in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Amgen
- 入组人数
- 610
- 试验地点
- 90
- 主要终点
- Number of Participants with Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women greater than or equal to 18 years old.
- •Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing performed according to in-country requirements. In the United States, this test must be performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
排除标准
- •Primary brain tumor.
- •Spinal cord compression, or untreated, or symptomatic, or active brain metastases, or leptomeningeal disease from non-brain tumors.
- •Myocardial infarction within 6 months of study day
- •Gastrointestinal (GI) tract disease causing the inability to take oral medication.
研究组 & 干预措施
Sotorasib + trametinib + panitumumab
Experimental: Sotorasib + trametinib + panitumumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
干预措施: Sotorasib (Drug)
Sotorasib + trametinib + panitumumab
Experimental: Sotorasib + trametinib + panitumumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
干预措施: Trametinib (Drug)
Sotorasib + trametinib + panitumumab
Experimental: Sotorasib + trametinib + panitumumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
干预措施: Panitumumab (Drug)
Sotorasib + RMC-4630
Experimental: Sotorasib + RMC-4630 Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants, with KRAS p.G12C mutant advanced solid tumors.
干预措施: Sotorasib (Drug)
Sotorasib + RMC-4630
Experimental: Sotorasib + RMC-4630 Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants, with KRAS p.G12C mutant advanced solid tumors.
干预措施: RMC-4630 (Drug)
Sotorasib + afatinib
Experimental: Sotorasib + afatinib Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
干预措施: Sotorasib (Drug)
Sotorasib + afatinib
Experimental: Sotorasib + afatinib Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
干预措施: Afatinib (Drug)
Sotorasib + panitumumab +/- chemotherapy
Experimental: Sotorasib + panitumumab +/- chemotherapy Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
干预措施: Sotorasib (Drug)
Sotorasib + panitumumab +/- chemotherapy
Experimental: Sotorasib + panitumumab +/- chemotherapy Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
干预措施: Panitumumab (Drug)
Sotorasib + panitumumab +/- chemotherapy
Experimental: Sotorasib + panitumumab +/- chemotherapy Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
干预措施: IV Chemotherapy (Regimen 1) (Drug)
Sotorasib + atezolizumab
Experimental: Sotorasib + atezolizumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
干预措施: Sotorasib (Drug)
Sotorasib + atezolizumab
Experimental: Sotorasib + atezolizumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
干预措施: Atezolizumab (Drug)
Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab
Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
干预措施: Sotorasib (Drug)
Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab
Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
干预措施: Pembrolizumab (Drug)
Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab
Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.
干预措施: Carboplatin, pemetrexed, docetaxel, paclitaxel (Drug)
Sotorasib Monotherapy
Experimental: Sotorasib only Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer with brain metastases.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer with brain metastases.
干预措施: Sotorasib (Drug)
Sotorasib + palbociclib
Experimental: Sotorasib + palbociclib Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.
干预措施: Sotorasib (Drug)
Sotorasib + palbociclib
Experimental: Sotorasib + palbociclib Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.
干预措施: Palbociclib (Drug)
Sotorasib + pembrolizumab
Experimental: Sotorasib + pembrolizumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant non small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS P.G12C mutant non small cell lung cancer.
干预措施: Sotorasib (Drug)
Sotorasib + pembrolizumab
Experimental: Sotorasib + pembrolizumab Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant non small cell lung cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS P.G12C mutant non small cell lung cancer.
干预措施: Pembrolizumab (Drug)
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy
Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.
干预措施: Sotorasib (Drug)
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy
Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.
干预措施: MVASI® (bevacizumab-awwb) (Drug)
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy
Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.
干预措施: IV Chemotherapy (Regimen 1) (Drug)
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy
Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.
干预措施: IV Chemotherapy (Regimen 2) (Drug)
Sotorasib + TNO155
Experimental: Sotorasib + TNO155 Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
干预措施: Sotorasib (Drug)
Sotorasib + TNO155
Experimental: Sotorasib + TNO155 Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.
干预措施: TNO155 (Drug)
Sotorasib + BI 1701963
Experimental: Sotorasib + BI 1701963 Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completion of dose exploration part of the study the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced non-small cell lung cancer and advanced colorectal cancer.
干预措施: Sotorasib (Drug)
Sotorasib + BI 1701963
Experimental: Sotorasib + BI 1701963 Dose Exploration and Dose Expansion
- Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
- Upon completion of dose exploration part of the study the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced non-small cell lung cancer and advanced colorectal cancer.
干预措施: BI 1701963 (Drug)
Sotorasib + AMG 404
Experimental: Sotorasib + AMG 404 Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors
干预措施: Sotorasib (Drug)
Sotorasib + AMG 404
Experimental: Sotorasib + AMG 404 Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors
干预措施: AMG 404 (Drug)
Sotorasib + everolimus
Experimental: Sotorasib + everolimus Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.
干预措施: Sotorasib (Drug)
Sotorasib + everolimus
Experimental: Sotorasib + everolimus Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.
干预措施: Everolimus (Drug)
结局指标
主要结局
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: 12 Months
Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: 12 Months
Number of Participants with Clinically Significant Changes in Vital Signs
时间窗: 12 Months
Number of Participants with Treatment-related Adverse Events
时间窗: 12 Months
Number of Participants with Clinically Significant Changes in ECG Measurements
时间窗: 12 Months
Number of Participants with Clinically Significant Changes in Laboratory Test Values
时间窗: 12 Months
次要结局
- Duration of Stable Disease(12 Months)
- Progression-free Survival(12 Months)
- Overall Survival(12 Months)
- Area Under the Plasma Concentration-time Curve (AUC)(12 Months)
- Disease Control Rate(12 Months)
- Time to Maximum Plasma Concentration (Tmax)(12 Months)
- Duration of Response(12 Months)
- Sotorasib Monotherapy Only: Intracranial Duration of Response(12 Months)
- Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS)(12 Months)
- Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS)(12 Months)
- Sotorasib + TNO155 Only: Best Overall Response(12 Months)
- Maximum Plasma Concentration (Cmax)(12 Months)
- Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs)(12 Months)
- Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values(12 Months)
- Objective Response Rate(12 Months)
- Time to Response(12 Months)
- Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels(12 Months)
- Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy(12 Months)
- Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS)(12 Months)
- Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs(12 Months)
- Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs)(12 Months)
- Sotorasib Monotherapy Only: Intracranial Objective Response Rate(12 Months)
- Sotorasib Monotherapy Only: Intracranial Disease Control Rate(12 Months)
- Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events(12 Months)
- Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements(12 Months)