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

Amgen

Status and phase: Active, not recruiting; Phase 1

Conditions: Kirsten Rat Sarcoma (KRAS) pG12C Mutation; Advanced Solid Tumors

Treatments: Drug: Pembrolizumab; Drug: IV Chemotherapy (Regimen 1); Drug: Panitumumab; Drug: Palbociclib; Drug: Trametinib; Drug: Everolimus; Drug: TNO155; Drug: BI 1701963; Drug: Atezolizumab; Drug: Sotorasib; Drug: MVASI® (bevacizumab-awwb); Drug: RMC-4630; Drug: IV Chemotherapy (Regimen 2); Drug: AMG 404; Drug: Afatinib; Drug: Carboplatin, pemetrexed, docetaxel, paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04185883

20190135

2023-506794-35 (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 610 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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610 participants in 14 patient groups

Sotorasib + trametinib + panitumumab

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Drug: Trametinib

Drug: Panitumumab

Sotorasib + RMC-4630

Experimental group

Description:

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.

Treatment:

Drug: RMC-4630

Drug: Sotorasib

Sotorasib + afatinib

Experimental group

Description:

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.

Treatment:

Drug: Afatinib

Drug: Sotorasib

Sotorasib + panitumumab +/- chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Drug: Panitumumab

Drug: IV Chemotherapy (Regimen 1)

Sotorasib + atezolizumab

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Drug: Atezolizumab

Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin, pemetrexed, docetaxel, paclitaxel

Drug: Sotorasib

Drug: Pembrolizumab

Sotorasib Monotherapy

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Sotorasib + palbociclib

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Drug: Palbociclib

Sotorasib + pembrolizumab

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Drug: Pembrolizumab

Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: IV Chemotherapy (Regimen 2)

Drug: MVASI® (bevacizumab-awwb)

Drug: Sotorasib

Drug: IV Chemotherapy (Regimen 1)

Sotorasib + TNO155

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Drug: TNO155

Sotorasib + BI 1701963

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Drug: BI 1701963

Sotorasib + AMG 404

Experimental group

Description:

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

Treatment:

Drug: AMG 404

Drug: Sotorasib

Sotorasib + everolimus

Experimental group

Description:

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.

Treatment:

Drug: Sotorasib

Drug: Everolimus