The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C +) advanced or metastatic non-small cell lung cancer (NSCLC).

Inclusion Criteria:

• Unequivocal histologically or cytologically confirmed diagnosis of metastatic or locally advanced NSCLC not amenable to treatment with surgical resection or combined chemoradiation
• Disease progression during or after treatment with at least one prior systemic therapy but no more than three lines of prior systemic therapy in the advanced or metastatic setting
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Documentation of the presence of a KRAS G12C mutation
• Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 (15 preferred) unstained, freshly cut, serial slides with an associated pathology report
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of >= 12 weeks

Exclusion Criteria:

• Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Known concomitant second oncogenic driver
• Mixed small-cell lung cancer or large cell neuroendocrine histology
• Known and untreated, or active central nervous system (CNS) metastases
• Leptomeningeal disease or carcinomatous meningitis
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently
• Any infection that, in the opinion of the investigator, could impact patient safety, or treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 of Cycle 1
• Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor
• More than 30 Gy of radiotherapy to the lung within 6 months of randomization
• Uncontrolled tumor-related pain
• Unresolved toxicities from prior anticancer therapy
• History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing