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Evaluating divarasib against other treatments for advanced lung cancer

A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Patients With Previously Treated KRAS G12C-Positive Advanced or Metastatic Non-Small Cell Lung Cancer

Phase 3 Interventional Hoffmann-La Roche · NCT06497556

This study is testing if a new drug called divarasib works better than existing treatments for advanced lung cancer in patients with a specific gene mutation.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment320 (estimated)
Ages18 Years and up
SexAll
SponsorHoffmann-La Roche Industry-sponsored
Locations244 sites (Gilbert, Arizona and 243 other locations)
Trial IDNCT06497556 on ClinicalTrials.gov

What this trial studies

This study assesses the safety and efficacy of divarasib compared to approved KRAS G12C inhibitors, sotorasib and adagrasib, in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have previously received treatment. Participants must have a confirmed KRAS G12C mutation and measurable disease, and they will be monitored for treatment outcomes. The study aims to determine if divarasib offers a better therapeutic option for this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced or metastatic NSCLC who have a confirmed KRAS G12C mutation and have undergone prior systemic therapy.

Not a fit: Patients with known hypersensitivity to divarasib, sotorasib, or adagrasib, or those with malabsorption syndrome may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with KRAS G12C-positive advanced lung cancer.

How similar studies have performed: Other studies have shown success with KRAS G12C inhibitors, indicating a promising approach in treating this specific mutation in lung cancer.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Unequivocal histologically or cytologically confirmed diagnosis of metastatic or locally advanced NSCLC not amenable to treatment with surgical resection or combined chemoradiation
* Disease progression during or after treatment with at least one prior systemic therapy but no more than three lines of prior systemic therapy in the advanced or metastatic setting
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Documentation of the presence of a KRAS G12C mutation
* Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 (15 preferred) unstained, freshly cut, serial slides with an associated pathology report
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of \>= 12 weeks

Exclusion Criteria:

* Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib
* Malabsorption syndrome or other condition that would interfere with enteral absorption
* Known concomitant second oncogenic driver
* Mixed small-cell lung cancer or large cell neuroendocrine histology
* Known and untreated, or active central nervous system (CNS) metastases
* Leptomeningeal disease or carcinomatous meningitis
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently
* Any infection that, in the opinion of the investigator, could impact patient safety, or treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 of Cycle 1
* Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor
* More than 30 Gy of radiotherapy to the lung within 6 months of randomization
* Uncontrolled tumor-related pain
* Unresolved toxicities from prior anticancer therapy
* History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer

Where this trial is running

Gilbert, Arizona and 243 other locations

+194 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-Small Cell Lung CancerKRAS G12C Lung CancerAdvanced Non-Small Cell Lung CancerKRAS G12 Lung CancerAdvanced Lung CancerMetastatic lung cancerDivarasibKRAS G12C Inhibitor
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.