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Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients
Trial Status: active
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.
Inclusion Criteria
Male or female patients ≥ 18 years of age
Histologic or cytologic evidence of NSCLC
Known KRAS G12C mutation
Either exposed or not exposed to a KRAS inhibitor to be included in Part A (avutometinib + sotorasib + defactinib) and not exposed to KRAS inhibitor to be included in Part B (avutometinib + sotorasib + defactinib), Cohort 1
Received at least 1 dose of a G12C inhibitor to be included in Part B, Cohort 2 (avutometinib + sotorasib + defactinib)
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
Additional locations may be listed on ClinicalTrials.gov for NCT05074810.
Locations matching your search criteria
United States
District of Columbia
Washington
MedStar Georgetown University Hospital
Status: Active
Name Not Available
Missouri
Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available
Ohio
Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Name Not Available
Texas
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
Status: Active
Name Not Available
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.