Clinical Trial

A Phase 1/2 Study of Avutometinib in Combination with Sotorasib with or without Defactinib in Patients with KRAS G12C mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 203) (VS-6766-203)

Brief Summary: 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.

Key Eligibility Criteria:

• Histologic/cytologic evidence of NSCLC, without histological evidence of a small cell component, that is metastatic (Stage 4)/locally advanced (Stage 3B-C)/unresectable)
• Known KRAS G12C mutation
• Either exposed or not exposed to a KRAS inhibitor to be included in Part A and not exposed to KRAS inhibitor to be included in Part B, Cohort 1
• Received at least 1 dose of a G12C inhibitor to be included in 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
• Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy excluded
• History of prior malignancy, with the exception of curatively treated malignancies excluded
• History of treatment with a direct and specific inhibitor of MEK excluded