A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer

Inclusion Criteria:

* Male or female subjects ≥ 18 years of age
* Histologic or cytologic evidence of NSCLC
* Known KRAS or BRAF mutation
* The subject must have received appropriate prior therapy
* 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 (excluding placement of vascular access)
* History of treatment with a direct and specific inhibitor of MEK, KRAS or BRAF except for treatment of BRAF V-600E mutant NSCLC
* Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 7 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
* Active skin disorder that has required systemic therapy within the past 1 year
* History of rhabdomyolysis
* Concurrent ocular disorders
* Concurrent heart disease or severe obstructive pulmonary disease
* Subjects with the inability to swallow oral medications