The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of single-agent divarasib or combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).
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
Known concomitant second oncogenic driver with available targeted treatment
Squamous cell histology NSCLC
Symptomatic, untreated, or actively progressing CNS metastases (Cohorts A, B, and C)
Prior treatment with a KRAS G12C inhibitor
Parallel
Divarasib
DrugParticipants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
Pembrolizumab
DrugParticipants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.
Carboplatin
DrugParticipants will receive IV carboplatin Q3W for four 21-day cycles.
Cisplatin
DrugParticipants will receive IV cisplatin Q3W for four 21-day cycles.
Pemetrexed
DrugParticipants will receive IV pemetrexed Q3W.
Percentage of Participants with Adverse Events (AEs)
Objective Response Rate (ORR)
The percentage of participants who experience a complete response or partial response, as determined by the investigator, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Duration of Response (DOR)
The time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Progression Free Survival (PFS)
The time from randomization, or date of first treatment for participants enrolled prior to the expansion stage, to the first occurrence of disease progression or death from any cause during the study (whichever occurs first), as determined by the investigator according to RECIST v1.1
Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Side Effects as Assessed Through the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
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