Tests divarasib alone or with other drugs in untreated lung cancer
Tests divarasib, alone or with other drugs, in adults with untreated KRAS G12C lung cancer.
Key facts
- Who runs it
- Hoffmann-La Roche
- Where
- Meldola, Milan, Orbassano, and Rome, ItalySee the 4 sitesAlso in 17 other countries, 67 sites
- Registry title
- 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
- Status
- Recruiting
- Phase
- Phase 1/2
- People taking part
- 320 people, planned
- Started
- 20 Jun 2023
- Expected to end
- 29 Jan 2032
- Type of study
- Interventional, 4 groups
- Treatments tested
- Divarasib
- Pembrolizumab
- Carboplatin
- Cisplatin
- Pemetrexed
- Record updated
- 5 November 2026
Who can take part
AI summary
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with advanced or metastatic non-small cell lung cancer with a KRAS G12C mutation who have not yet had systemic treatment for it.
- Age
- 18 years or older.
- Sex
- All sexes can join.
- Disease stage
- Non-small cell lung cancer that is locally advanced and cannot be removed by surgery, or has spread. It must be measurable on scans. Squamous cell type is not allowed.
- Earlier treatment
- No earlier systemic treatment for advanced or metastatic lung cancer. No earlier treatment with a KRAS G12C inhibitor.
- Biomarker or test result
- The tumor must have a KRAS G12C mutation (confirmed biomarker). A tumor tissue sample with a pathology report is needed.
Main reasons for not taking part
- Another known cancer-driving gene change that has a targeted treatment
- Squamous cell type of lung cancer
- Brain metastases that cause symptoms, are untreated or are getting worse (Cohorts A, B and C)
- Another cancer within the past 5 years, with some exceptions
- History of lung conditions such as pulmonary fibrosis or pneumonitis, or active tuberculosis
The registry criteria, word for word
Show all 17 criteriaShow less
Who can take part
- 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
Who cannot take part
- Known concomitant second oncogenic driver with available targeted treatment
- Prior treatment with a KRAS G12C inhibitor
- 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
- 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
- Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)
- 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
- Squamous cell histology NSCLC
- Symptomatic, untreated, or actively progressing CNS metastases (Cohorts A, B, and C)
- Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia
Where in Italy
Also in 17 other countries, 67 sites
- Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.lMeldola, ItalyTaking people
- Fondazione IRCCS - Istituto Nazionale dei TumoriMilan, ItalyTaking people
- Azienda Ospedaliero-Universitaria San Luigi GonzagaOrbassano, ItalyTaking people
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSRome, ItalyTaking people
About the trial
What the trial wants to find out
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).
The 4 groups in the trial
- Cohort A - Combination Dose Finding + Dose ExpansionTreatment being tested
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.
Treatment: Divarasib and Pembrolizumab
- Cohort B - Combination Dose Finding + Dose ExpansionTreatment being tested
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.
Treatment: Divarasib, Pembrolizumab, Carboplatin, Cisplatin, and Pemetrexed
- Cohort C - Dose ExpansionTreatment being tested
Participants enrolled in this cohort will receive one dose level of divarasib QD.
Treatment: Divarasib
- Cohort D - Dose ExpansionTreatment being tested
Participants enrolled in this cohort will receive one dose level of divarasib QD.
Treatment: Divarasib
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorData and sources
- Registry record
- Listed on ClinicalTrials.gov and on the EU's official list of trials (CTIS).
- Official 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
- Plain-language title
- Tests divarasib alone or with other drugs in untreated lung cancerGenerated from the registry record. The registry title is the official one.
- AI summary
- From the trial's eligibility criteria. Read by machine on 12 November 2026.
- Record updated
- 5 November 2026