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

Recruiting now · Phase 1/Phase 2

Conditions studied: Non-Small Cell Lung Cancer

In brief

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).

Key facts

Study ID

NCT05789082

Run by

Hoffmann-La Roche

People needed

320

Starts

2023-06-20

Expected to finish

2032-01-29

Last updated by the study team

2026-07-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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 it is running

• Ottawa Hospital Regional Cancer Centre — Ottawa, Ontario, Canada (enrolling)
• Jewish General Hospital — Montreal, Quebec, Canada (enrolling)
• AZ Delta (Campus Rumbeke) — Roeselare, Belgium (enrolling)
• Instituto do Cancer do Estado de Sao Paulo - ICESP — São Paulo, São Paulo, Brazil (enrolling)
• Yale Cancer Center — New Haven, Connecticut, United States (enrolling)
• Florida Cancer Specialists - SOUTH - SCRI - PPDS — Fort Myers, Florida, United States (enrolling)
• Florida Cancer Specialists - NORTH - SCRI - PPDS — St. Petersburg, Florida, United States (enrolling)
• Florida Cancer Specialists - EAST - SCRI - PPDS — West Palm Beach, Florida, United States (enrolling)
• Hospital de Cancer de Barretos — Barretos, São Paulo, Brazil (enrolling)
• NYU Cancer Center — New York, New York, United States (enrolling)
• Mount SInai Medical Center — New York, New York, United States (enrolling)
• Montefiore Medical Center - Montefiore Medical Park — The Bronx, New York, United States (enrolling)
• MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
• Oncology & Hematology Associates of Southwest Virginia, Inc — Blacksburg, Virginia, United States (enrolling)
• Virginia Oncology Associates — Norfolk, Virginia, United States (enrolling)
• Hospital Britanico — Buenos Aires, Argentina (enrolling)
• Clinica Adventista Belgrano — Ciudad Autonoma Buenos Aires, Argentina (enrolling)
• Centro Oncologico Riojano Integral (CORI) — La Rioja, Argentina (enrolling)
• NYU Langone Hospital - Long Island — Mineola, New York, United States (enrolling)
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (enrolling)
• Alfred Health — Melbourne, Victoria, Australia (enrolling)
• Cliniques Universitaires St-Luc — Brussels, Belgium (enrolling)
• Jessa Zkh (Campus Virga Jesse) — Hasselt, Belgium (enrolling)
• Clinique Ste-Elisabeth — Namur, Belgium (enrolling)
• Harbin Medical University Cancer Hospital — Harbin, China (enrolling)

Full record on ClinicalTrials.gov

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