Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

Phase 1

Recruiting

• Conditions: Advanced Solid Tumors; Kirsten Rat Sarcoma (KRAS) pG12C Mutation
• Interventions: Drug: Sotorasib; Drug: RMC-4630; Drug: Afatinib; Drug: MVASI® (bevacizumab-awwb); Drug: Atezolizumab; Drug: BI 1701963; Drug: AMG 404; Drug: TNO155; Drug: Trametinib; Drug: Pembrolizumab; Drug: Palbociclib; Drug: Everolimus; Drug: IV Chemotherapy (Regimen 1); Drug: Carboplatin, pemetrexed, docetaxel, paclitaxel; Drug: Panitumumab; Drug: IV Chemotherapy (Regimen 2)

• Registration Number: NCT04185883
• Lead Sponsor: Amgen

Brief Summary

To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-03
• Study First Submitted QC: 2019-12-03
• Study First Posted: 2019-12-04
• Study Start: 2019-12-17
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-03-27
• Primary Completion: 2026-06-16
• Study Completion: 2027-12-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

• 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.

Exclusion Criteria

• 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 1.
• Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Sotorasib + RMC-4630	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.
Sotorasib + trametinib + panitumumab	Sotorasib	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.
Sotorasib + afatinib	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.
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy	MVASI® (bevacizumab-awwb)	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.
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy	IV Chemotherapy (Regimen 1)	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.
Sotorasib + afatinib	Sotorasib	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.
Sotorasib + atezolizumab	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.
Sotorasib + panitumumab +/- chemotherapy	IV Chemotherapy (Regimen 1)	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.
Sotorasib + BI 1701963	Sotorasib	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.
Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab	Carboplatin, pemetrexed, docetaxel, paclitaxel	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.
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy	IV Chemotherapy (Regimen 2)	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.
Sotorasib + BI 1701963	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.
Sotorasib + AMG 404	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
Sotorasib + TNO155	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.
Sotorasib + trametinib + panitumumab	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.
Sotorasib + trametinib + panitumumab	Trametinib	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.
Sotorasib + RMC-4630	Sotorasib	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.
Sotorasib + panitumumab +/- chemotherapy	Sotorasib	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.
Sotorasib + panitumumab +/- chemotherapy	Panitumumab	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.
Sotorasib + atezolizumab	Sotorasib	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.
Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab	Sotorasib	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.
Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab	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.
Sotorasib Monotherapy	Sotorasib	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.
Sotorasib + palbociclib	Sotorasib	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.
Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy	Sotorasib	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.
Sotorasib + palbociclib	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.
Sotorasib + pembrolizumab	Sotorasib	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.
Sotorasib + pembrolizumab	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.
Sotorasib + TNO155	Sotorasib	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.
Sotorasib + AMG 404	Sotorasib	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
Sotorasib + everolimus	Sotorasib	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.
Sotorasib + everolimus	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	12 Months
Number of Participants with Clinically Significant Changes in ECG Measurements	12 Months
Number of Participants with Dose Limiting Toxicities (DLTs)	12 Months
Number of Participants with Clinically Significant Changes in Vital Signs	12 Months
Number of Participants with Treatment-related Adverse Events	12 Months
Number of Participants with Clinically Significant Changes in Laboratory Test Values	12 Months

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-time Curve (AUC)	12 Months
Sotorasib Monotherapy Only: Intracranial Disease Control Rate	12 Months	Intracranial disease control rate assessed per RANO-BM.
Progression-free Survival	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	Intracranial duration of response assessed per RANO-BM.
Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS)	12 Months	Intracranial PFS assessed per RANO-BM.
Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS)	12 Months	Non-intracranial PFS assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Sotorasib + TNO155 Only: Best Overall Response	12 Months
Maximum Plasma Concentration (Cmax)	12 Months
Duration of Stable Disease	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	Overall PFS assessed per RECIST 1.1 and RANO-BM.
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	Intracranial objective response rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).
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
Overall Survival	12 Months

Trial Locations

Locations (90)

Arizona Oncology Associates Professional Corporation; 🇺🇸 Tucson, Arizona, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

University of California San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Loma Linda University Cancer Center; 🇺🇸 Loma Linda, California, United States

University of Southern California, Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

University of California Davis Medical Center; 🇺🇸 Sacramento, California, United States

University of California San Francisco Mission Bay Campus; 🇺🇸 San Francisco, California, United States

University of California Los Angeles; 🇺🇸 Santa Monica, California, United States

Rocky Mountain Cancer Centers Denver Midtown; 🇺🇸 Denver, Colorado, United States

Sarah Cannon Research Institute; 🇺🇸 Denver, Colorado, United States

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