A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC

Inclusion Criteria: * Age ≥ 18 years. * Willing and able to give written informed consent. * Have histologically or cytologically confirmed NSCLC, with presence of EGFR mutation(s) sensitive to EGFR inhibitors, or KRAS G12C mutation. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Adequate bone marrow and organ function. * Have ECOG performance status of 0 or 1. * Willing to comply with all protocol-required visits, assessments, and procedures. * Able to swallow oral medication. Exclusion Criteria: * Concurrent treatment with any systemic anticancer therapy for NSCLC, including any approved or investigational agent. * For participants with EGFRm NSCLC: prior therapy with a RAS, RAF, MEK, or ERK inhibitor. * For participants with KRAS G12Cm NSCLC: prior therapy with a SHP2, ERK, or KRAS G12C inhibitor (depending on which cohort is being considered for enrollment). * Palliative radiotherapy within 7 days of enrollment. * History of unacceptable toxicity to treatment with osimertinib or sotorasib. * Major surgery within the 28 days of enrollment. * Unresolved toxicities from prior systemic therapy greater than NCI CTCAE grade 1 at time of enrollment, except for toxicities not considered a safety risk (eg, alopecia, vitiligo, and grade 2 neuropathy due to prior chemotherapy). * History of another malignancy ≤5 years prior to first dose, except for patients who are disease-free for \>2 years after treatment with curative intent or who have carcinoma in situ. * Symptomatic and unstable brain metastases, or spinal cord compression, except for patients who have completed definitive therapy (surgery or radiotherapy), are not on steroids, and have a stable neurologic status for a least 2 weeks after completion of the definitive therapy and steroids. * History of or clinically active ILD, drug induced ILD, or radiation pneumonitis that required steroid treatment. * Impaired cardiovascular function or clinically significant cardiovascular disease. * History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO. * Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study. * Pregnant or breastfeeding women. * Contraindication to osimertinib or sotorasib use as per local label.