Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients

Inclusion Criteria:

* Male or female subjects ≥ 18 years of age
* Histologic or cytologic evidence of NSCLC
* Known KRAS G12C mutation
* The subject must have received prior therapy with a KRAS G12C inhibitor and experienced progression
* Must have received appropriate treatment with at least one prior systemic regimen, but no more than 3 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:

* Prior chemotherapy, targeted therapies, radiotherapy, immunotherapy or treatment with an investigational agent within 14 days of receipt of study drug (within 6 weeks for nitrosoureas, mitomycin C and chest radiation; within 6 months prior to Cycle 1 Day 1 for chest radiation \> 30Gy)
* History of prior malignancy, with the exception of curatively treated malignancies
* Major surgery within 4 weeks (excluding placement of vascular access)
* Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
* Exposure to strong inhibitors of breast cancer resistance protein (BCRP) within 14 days prior to the first dose and during the course of therapy
* Symptomatic brain metastases requiring steroids or other local interventions within the 2 weeks prior to initiation of therapy
* 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 1 year
* History of rhabdomyolysis or interstitial lung disease
* Concurrent ocular disorders
* Concurrent heart disease or severe obstructive pulmonary disease
* Subjects with the inability to swallow oral medications