Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients
Purpose
This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.
Conditions
- Non Small Cell Lung Cancer
- KRAS Activating Mutation
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male or female patients ≥ 18 years of age - Histologic or cytologic evidence of NSCLC - Known KRAS G12C mutation - Have not received a KRAS inhibitor to be included in Part A (avutometinib + sotorasib) and Part B (avutometinib + sotorasib + defactinib), Cohort 1 - Received at least 1 dose of a G12C inhibitor to be included in Part A (avutometinib + sotorasib + defactinib) and Part B, Cohort 2 - Must have received appropriate treatment with at least one prior systemic regimen, but no more than 2 prior regimens, for Stage 3B-C or 4 NSCLC - Measurable disease according to RECIST 1.1 - An Eastern Cooperative Group (ECOG) performance status ≤ 1 - Adequate organ function - Adequate recovery from toxicities related to prior treatments - Agreement to use highly effective method of contraceptive
Exclusion Criteria
- Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy - History of prior malignancy, with the exception of curatively treated malignancies - Major surgery within 4 weeks, minor surgery within 2 weeks (excluding placement of vascular access) - History of treatment with a direct and specific inhibitor of MEK - Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy - Symptomatic brain metastases requiring steroids or other local interventions. - Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy - Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active - Active skin disorder that has required systemic therapy within the past year - History of rhabdomyolysis - Concurrent ocular disorders - Concurrent heart disease or severe obstructive pulmonary disease - Inability to swallow oral medications - Female patients that are pregnant or breastfeeding - Previously treated with sotorasib and were dose reduced due to toxicity
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental avutometinib (VS-6766)+sotorasib |
To determine the recommended phase 2 dose (RP2D) for avutometinib (VS 6766) in combination with sotorasib in KRAS G12C inhibitor naïve and exposed patients |
|
|
Experimental avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor naïve |
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients |
|
|
Experimental avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor exposed |
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients |
|
|
Experimental avutometinib (VS-6766)+sotorasib+defactinib |
To determine the recommended phase 2 dose (RP2D) for avutometinib (VS-6766) in combination with sotorasib and defactinib in KRAS G12C inhibitor exposed patients |
|
|
Experimental avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor naive |
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients |
|
|
Experimental avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor exposed |
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients |
|
Recruiting Locations
MedStar Washington Hospital Center, MedStar Georgetown Cancer Institute,
Washington, District of Columbia 20010
Washington, District of Columbia 20010
Georgetown University Medical Center
Washington, District of Columbia 20007
Washington, District of Columbia 20007
More Details
- Status
- Recruiting
- Sponsor
- Verastem, Inc.
Detailed Description
This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C mutant NSCLC.