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Evaluating divarasib with other cancer therapies for advanced lung cancer with a KRAS mutation

A Phase Ib/II, Open-Label, Multicenter Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Patients With Previously Untreated Advanced Or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation

PHASE1; PHASE2 · Hoffmann-La Roche · NCT05789082

This study is testing if a new cancer drug called divarasib, when combined with other treatments, can help people with advanced lung cancer that has a specific KRAS mutation feel better and improve their outcomes.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment320 (estimated)
Ages18 Years and up
SexAll
SponsorHoffmann-La Roche (industry)
Drugs / interventionspembrolizumab
Locations71 sites (Duarte, California and 70 other locations)
Trial IDNCT05789082 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, pharmacokinetics, and activity of divarasib when combined with other anti-cancer therapies in patients with previously untreated advanced or metastatic non-small cell lung cancer (NSCLC) that has a KRAS G12C mutation. Participants will receive divarasib alongside treatments such as pembrolizumab, carboplatin, cisplatin, and pemetrexed. The study aims to determine how well this combination works and its safety profile in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals with previously untreated advanced or metastatic non-small cell lung cancer with a confirmed KRAS G12C mutation.

Not a fit: Patients with known concomitant second oncogenic drivers that have available targeted treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with advanced lung cancer harboring the KRAS G12C mutation.

How similar studies have performed: Other studies have shown promise in targeting KRAS mutations in lung cancer, indicating that this approach may be viable and beneficial.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Duarte, California and 70 other locations

+21 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Non-Small Cell Lung Cancer

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.