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RecruitingLast updated: 15 April 2026

BO44426: Targeted therapy is in combination with other anti-cancer therapies in people with previously untreated, advanced or metastatic non-small cell lung cancer with a KRAS G12C mutationA 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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Lung Cancers Lung cancer

Age

People18+

Trial acronym

BO44426

Clinical summary

Summary

This study is recruiting people with locally advanced, unresectable or metastatic non-small cell lung cancer that is not eligible for curative surgery and/or definitive chemotherapy. You should not have had prior systemic treatment for your advanced unresectable or metastatic disease. Prior treatment when the cancer was at an earlier stage may be permitted.

This study has four cohorts.

Cohort A: Combination Dose Finding + Dose Expansion
Participants in the Dose Finding part will receive divarasib targeted therapy by mouth (orally) once a day. Different dose levels of divarasib will be studied to help researchers learn which dose works best.

Participants in this cohort will also receive pembrolizumab immunotherapy, which is given as in intravenous (IV) infusion once every 3 weeks.

During the Dose Expansion part, participants will be randomly assigned (by chance) to receive one of two different dose levels of divarasib, both given together with pembrolizumab.

Cohort B: Combination Dose Finding + Dose Expansion
Participants enrolled in this cohort will receive oral divarasib once a day (different dose levels will be studied) with pembrolizumab via IV every 3 weeks. Participants will also receive investigator's choice of platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed.

Cohort C: Dose Expansion
Participants in this cohort will receive one dose level of divarasib orally once a day.

Cohort D: Dose Expansion
Participants will receive one dose level of divarasib orally once a day.

 

Conditions

This trial is treating people with locally advanced, metastatic or unresectable non-small cell lung cancer

Eligibility

Inclusion

  • 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

  • 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

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body, but it is not possible to perform surgery to remove it (unresectable).

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

  • NCT05789082 *
  • 2022-003048-28; 2023-507171-22-00 *
  • BO44426

Trial sponsor

Hoffmann-La Roche

Scientific Title

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

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