Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients

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