Recruiting
Phase 1
Phase 2

Divarasib, Anti-Cancer Therapies

Sponsor:

Hoffmann-La Roche

Code:

NCT05789082

Conditions

Non-Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Divarasib

Pembrolizumab

Carboplatin

Cisplatin

Pemetrexed

Study Details

Brief summary:

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).

Conditions

Non-Small Cell Lung Cancer

Study ID

NCT05789082

Start date

Jun 20, 2023

Status verified date

Sep, 2026

Completion date

Jan 29, 2032

Anticipated

Primary completion date

Jan 29, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

320 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort A - Combination Dose Finding + Dose Expansion

Participants will be enrolled in different cohorts to receive divarasib (different dose levels will be evaluated) once a day (QD) combined with pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W).

During the expansion stage, some participants are planned to be randomized to one divarasib combination dose level; other participants are planned to be randomized to another divarasib combination dose level. Divarasib will be given in combination with pembrolizumab.

experimental: Cohort B - Combination Dose Finding + Dose Expansion

Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) QD combined with pembrolizumab 200 mg IV Q3W plus investigator's choice of platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed.

experimental: Cohort C - Dose Expansion

Participants enrolled in this cohort will receive one dose level of divarasib QD.

experimental: Cohort D - Dose Expansion

Participants enrolled in this cohort will receive one dose level of divarasib QD.

Interventions

Divarasib

Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.

Pembrolizumab

Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.

Carboplatin

Participants will receive IV carboplatin Q3W for four 21-day cycles.

Cisplatin

Participants will receive IV cisplatin Q3W for four 21-day cycles.

Pemetrexed

Participants will receive IV pemetrexed Q3W.

Primary outcome measure

  • Percentage of Participants with Adverse Events (AEs) [ Time Frame: Baseline until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 5 years) ]

Central Contacts and Locations

Central contacts

Reference Study ID Number: BO44426 https://forpatients.roche.com/ No attachments to email below.

888-662-6728 (U.S. and Canada)global-roche-genentech-trials@gene.com

Locations

Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06520

Florida Cancer Specialists - SOUTH - SCRI - PPDS

Recruiting

Fort Myers, Florida, United States, 33901-8108

Florida Cancer Specialists - NORTH - SCRI - PPDS

Recruiting

St. Petersburg, Florida, United States, 33705-1400

Florida Cancer Specialists - EAST - SCRI - PPDS

Recruiting

West Palm Beach, Florida, United States, 33401-3406

NYU Langone Hospital - Long Island

Recruiting

Mineola, New York, United States, 11501

NYU Cancer Center

Recruiting

New York, New York, United States, 10016

Mount SInai Medical Center

Recruiting

New York, New York, United States, 10029

Montefiore Medical Center - Montefiore Medical Park

Recruiting

The Bronx, New York, United States, 10461

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Oncology & Hematology Associates of Southwest Virginia, Inc

Recruiting

Blacksburg, Virginia, United States, 24060

Virginia Oncology Associates

Recruiting

Norfolk, Virginia, United States, 23502

Ottawa Hospital Regional Cancer Centre

Recruiting

Ottawa, Ontario, Canada, K1H 8M2

Jewish General Hospital

Recruiting

Montreal, Quebec, Canada, H3T 1E2

More Information

Sponsor

Hoffmann-La Roche

Last update posted

Sep 8, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-11. This information was provided to ClinicalTrials.gov by Hoffmann-La Roche on 2026-09-08.