RecruitingPhase 1 / Phase 2NCT05789082

A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation

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).

Checked against the public recordLast updated Aug 10, 2026 · Source: ClinicalTrials.gov

StatusRecruiting
PhasePhase 1 / Phase 2
U.S. locations71
SponsorHoffmann-La Roche
01
Study overview

What this study is about

Purpose
Treatment
Study type
Interventional
Phase
Phase 1 / Phase 2
Sponsor
Hoffmann-La Roche
Interventions being studied
Drug: Divarasib; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed
02
Explore related studies

How this study is categorized

These labels come from structured fields and exact terms in the public record.

03
Public criteria

Who may be able to participate

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. Additionally, for participants in cohort D, measurable brain metastases defined as at least 5 millimeters and twice the slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment. Exclusion Criteria: * 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 * 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 * Co-morbid condition that is an absolute contraindication to treatment with corticosteroids * Inability or unwillingness to take prophylactic treatments such as corticosteroids, anti-emetics, folic acid, or vitamin B12 supplementation. * Participants with brain metastases for whom complete surgical resections is clinically appropriate

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

04
Study sites

U.S. locations

  • City of Hope National Medical CenterDuarte, California
  • City of Hope - SeacliffHuntington Beach, California
  • City of Hope at Irvine LennarIrvine, California
  • UCSD Moores Cancer CenterLa Jolla, California
  • City of Hope - Long Beach ElmLong Beach, California
  • Yale Cancer CenterNew Haven, Connecticut
  • Florida Cancer Specialists - SOUTH - SCRI - PPDSFort Myers, Florida
  • Florida Cancer Specialists - NORTH - SCRI - PPDSSt. Petersburg, Florida
  • Florida Cancer Specialists - EAST - SCRI - PPDSWest Palm Beach, Florida
  • NYU Langone Hospital - Long IslandMineola, New York
  • NYU Cancer CenterNew York, New York
  • Mount SInai Medical CenterNew York, New York

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Aug 10, 2026. Always confirm current availability with the study team.

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