Phase 1/2 Study of Avutometinib (VS-6766) and Sotorasib, With or Without Defactinib, for KRAS G12C Non-Small Cell Lung Cancer Patients

Inclusion Criteria

• Must be 18 years or older.
• Have a confirmed diagnosis of Non-Small Cell Lung Cancer (NSCLC).
• Have a known KRAS G12C mutation.
• For Part A and Part B, Cohort 1: Have not received a KRAS inhibitor before.
• For Part A and Part B, Cohort 2: Have received at least one dose of a G12C inhibitor before.
• Must have received at least one, but no more than two, previous treatments for advanced NSCLC.
• Have measurable disease according to specific medical criteria.
• Have a performance status score of 0 or 1, indicating full activity or some restriction in strenuous activities.
• Have adequate organ function and recovery from previous treatment side effects.
• Agree to use a highly effective method of contraception.

Exclusion Criteria

• Have received systemic anti-cancer therapy within 4 weeks before starting the study treatment.
• Have a history of another cancer, unless it was treated and cured.
• Have had major surgery within 4 weeks or minor surgery within 2 weeks before starting the study treatment.
• Have been treated with a specific type of drug called a MEK inhibitor.
• Have used certain medications that affect liver enzymes within 14 days before starting the study treatment.
• Have brain metastases that require treatment with steroids or other interventions.
• Have had a COVID-19 infection within 28 days before starting the study treatment.
• Have active hepatitis B, hepatitis C, or HIV infection.
• Have an active skin disorder that required treatment within the past year.
• Have a history of a muscle condition called rhabdomyolysis.
• Have eye disorders or severe heart or lung disease.
• Cannot swallow pills.
• Are pregnant or breastfeeding.
• Have previously been treated with sotorasib and had to reduce the dose due to side effects.