Description:
To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.
Clinical Trials /
Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
NCT04185883
Related Conditions:
- Colorectal Carcinoma
- Malignant Solid Tumor
- Non-Small Cell Lung Carcinoma
Recruiting Status:
Recruiting
Phase:
Phase 1/Phase 2
Trial Eligibility
Document
Title
- Brief Title: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
- Official Title: A Phase 1b/2, 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)
Clinical Trial IDs
- ORG STUDY ID: 20190135
- NCT ID: NCT04185883
Conditions
- Advanced Solid Tumors
- Kirsten Rat Sarcoma (KRAS) pG12C Mutation
Interventions
| Drug | Synonyms | Arms |
|---|---|---|
| Sotorasib | Sotorasib + AMG 404 | |
| AMG 404 | Sotorasib + AMG 404 | |
| trametinib | Sotorasib + trametinib | |
| RMC-4630 | Sotorasib + RMC-4630 | |
| afatinib | Sotorasib + afatinib | |
| pembrolizumab | Sotorasib + pembrolizumab | |
| panitumumab | Sotorasib + panitumumab +/- FOLFIRI | |
| carboplatin, pemetrexed, docetaxel | Sotorasib + MVASI® (bevacizumab-awwb)+ FOLFIRI or FOLFOX | |
| atezolizumab | Sotorasib + atezolizumab | |
| everolimus | Sotorasib + everolimus | |
| palbociclib | Sotorasib + palbociclib | |
| MVASI® (bevacizumab-awwb) | Sotorasib + MVASI® (bevacizumab-awwb)+ FOLFIRI or FOLFOX |
Purpose
To evaluate the safety and tolerability of sotorasib administered in investigational regimens
in adult participants with KRAS p.G12C mutant advanced solid tumors.
Trial Arms
| Name | Type | Description | Interventions |
|---|---|---|---|
| Sotorasib + trametinib | Experimental | Experimental: Sotorasib + trametinib 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 | Experimental | 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 + RMC-4630 | Experimental | 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 + afatinib | Experimental | Experimental:Sotorasib + afatinib Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant 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 + pembrolizumab | Experimental | Experimental: Sotorasib + 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 + panitumumab +/- FOLFIRI | Experimental | Experimental: Sotorasib + panitumumab +/- FOLFIRI 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 | 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, pemetraxed, docetaxel | Experimental | Experimental: Sotorasib + carboplatin, pemetraxed, docetaxel 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 | Experimental | 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 | Experimental | 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 + everolimus | Experimental | 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 + trametinib+ panitumumab | Experimental | 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 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)+ FOLFIRI or FOLFOX | Experimental | Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ FOLFIRI or FOLFOX 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. |
|
Eligibility Criteria
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.
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.
| Maximum Eligible Age: | 100 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
Secondary Outcome Measures
| Measure: | Phase 1b: Maximum Plasma Concentration (Cmax) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Time to Maximum Plasma Concentration (Tmax) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Area Under the Plasma Concentration-time Curve (AUC) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Objective Response Rate |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Disease Control Rate |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Duration of Response |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Progression-free Survival |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Duration of Stable Disease |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Time to Response |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Overall Survival |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Sotorasib Monotherapy Only: Intracranial Objective Response Rate |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: | Intracranial objective response rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM). |
| Measure: | Phase 1b: Sotorasib Monotherapy Only: Intracranial Disease Control Rate |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: | Intracranial disease control rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM). |
| Measure: | Phase 1b: Sotorasib Monotherapy Only: Intracranial Duration of Response |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: | Intracranial duration of response assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM). |
| Measure: | Phase 1b: Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 1b: Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: | Intracranial PFS assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM) |
| Measure: | Phase 1b: Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: | Non-intracranial PFS assessed per RECIST 1.1. |
| Measure: | Phase 1b: Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: | Overall PFS assessed per RECIST 1.1 and RANO-BM. |
| Measure: | Phase 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Number of Participants with Grade ≥3 Treatment-emergent Adverse Events (TEAEs) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Maximum Plasma Concentration (Cmax) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Time to Maximum Plasma Concentration (Tmax) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Area Under the Plasma Concentration-time Curve (AUC) |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Disease Control Rate |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Duration of Response |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Progression-free Survival |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Time to Response |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
| Measure: | Phase 2: Overall Survival |
| Time Frame: | 12 Months |
| Safety Issue: | |
| Description: |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Amgen |
Last Updated
August 13, 2021
