NCT05789082Recruiting
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
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).
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
Contacts
The trial team's contact details are shown on request.
See the official trial record- Status
- Recruiting
- Phase
- Phase 1 · Phase 2
- Study type
- Interventional
- Countries
- Switzerland, Italy, United States, Argentina, Australia, Belgium, Brazil, Canada, China, Israel, Japan, Netherlands, Poland, South Korea, Spain, Sweden, Taiwan, United Kingdom
- Sponsor
- Hoffmann-La Roche(Industry)
- Protocol no.
- BO44426
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Drug
Treatments studied
- Divarasib
- Pembrolizumab
- Carboplatin
- Cisplatin
- Pemetrexed
Locations · 57
- Basel, SwitzerlandUniversitätsspital BaselRecruiting at this site
- Milan, ItalyIrccs Istituto Nazionale Dei Tumori (Int)Recruiting at this site
- Orbassano, ItalyA.O. Universitaria S. Luigi GonzagaRecruiting at this site
- New Haven, United StatesYale Cancer CenterRecruiting at this site
- Fort Myers, United StatesFlorida Cancer Specialists - SOUTH - SCRI - PPDSRecruiting at this site
- St. Petersburg, United StatesFlorida Cancer Specialists - NORTH - SCRI - PPDSRecruiting at this site
- West Palm Beach, United StatesFlorida Cancer Specialists - EAST - SCRI - PPDSRecruiting at this site
- Mineola, United StatesNYU Langone Hospital - Long IslandRecruiting at this site
- New York, United StatesNYU Cancer CenterRecruiting at this site
- New York, United StatesMount SInai Medical CenterRecruiting at this site
- The Bronx, United StatesMontefiore Medical Center - Montefiore Medical ParkRecruiting at this site
- Houston, United StatesMD Anderson Cancer CenterRecruiting at this site
- Blacksburg, United StatesOncology & Hematology Associates of Southwest Virginia, IncRecruiting at this site
- Norfolk, United StatesVirginia Oncology AssociatesRecruiting at this site
- Buenos Aires, ArgentinaHospital BritanicoRecruiting at this site
- Ciudad Autonoma Buenos Aires, ArgentinaClinica Adventista BelgranoRecruiting at this site
- La Rioja, ArgentinaCentro Oncologico Riojano Integral (CORI)Recruiting at this site
- Melbourne, AustraliaPeter MacCallum Cancer CentreRecruiting at this site
- Melbourne, AustraliaAlfred HealthRecruiting at this site
- Brussels, BelgiumCliniques Universitaires St-LucRecruiting at this site
- Hasselt, BelgiumJessa Zkh (Campus Virga Jesse)Recruiting at this site
- Namur, BelgiumClinique Ste-ElisabethRecruiting at this site
- Roeselare, BelgiumAZ Delta (Campus Rumbeke)Recruiting at this site
- Barretos, BrazilHospital de Cancer de BarretosRecruiting at this site
- São Paulo, BrazilInstituto do Cancer do Estado de Sao Paulo - ICESPRecruiting at this site
- Ottawa, CanadaOttawa Hospital Regional Cancer CentreRecruiting at this site
- Montreal, CanadaJewish General HospitalRecruiting at this site
- Changsha, ChinaHunan Cancer HospitalRecruiting at this site
- Harbin, ChinaHarbin Medical University Cancer HospitalRecruiting at this site
- Shanghai, ChinaShanghai Pulmonary HospitalRecruiting at this site
In total, worldwide, 57 of the 71 sites listed in the registry are recruiting; the other 14 are not currently recruiting.
Site status per the ClinicalTrials.gov registry (last update posted: October 6, 2026).
This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.
+ 27 more locations
Other identifiers
- 2022-003048-28 · EudraCT number
- 2023-507171-22-00 · CTIS number
- 2023 · NIH grant
See also
Other versions
These results are indicative and do not replace medical advice — discuss them with your doctor.