Cancer Clinical Research Unit

Inclusion Criteria: - Confirmation of Biomarker eligibility - Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor. - Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 - Histologically or cytologically documented locally advanced unresectable or metastatic NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy - No prior systemic treatment for advanced unresectable or metastatic NSCLC - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Exclusion Criteria: - Known concomitant second oncogenic driver with available targeted treatment - Squamous cell histology NSCLC - Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases - Prior treatment with a KRAS G12C inhibitor - Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only) - History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, active tuberculosis, significant cardiovascular disease within 3 months prior to initiation of study treatment - History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer - Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia