The Roche divarasib Phase 3 trial reported that the experimental KRAS G12C inhibitor cut the risk of death by 44% compared with two approved drugs in people with previously treated non-small cell lung cancer. The KRASCENDO 1 results, presented at the ESMO 2026 congress on 25 October and published in the New England Journal of Medicine, showed median overall survival of 17.7 months with divarasib versus 12.0 months with the comparators. Divarasib remains investigational and is not approved anywhere.
Key takeaways from the Roche divarasib Phase 3 trial
- Overall survival hazard ratio was 0.56 (95% confidence interval 0.41 to 0.78), which is the 44% reduction in the risk of death, at a first interim analysis.
- Median overall survival was 17.7 months with divarasib versus 12.0 months with sotorasib or adagrasib.
- Confirmed objective response rate was 58% versus 32%.
- Median progression-free survival was 9.8 months versus 5.7 months (hazard ratio 0.58).
- The trial enrolled 338 patients; divarasib is investigational and no filing timeline has been disclosed.
Who was studied in the Roche divarasib Phase 3 trial
KRASCENDO 1 (NCT06497556) is a global, open-label, randomised Phase 3 trial in adults with locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer who had already received prior treatment. A total of 338 patients were randomised. One group received divarasib 400 mg once daily. The other received an approved KRAS G12C inhibitor chosen by the investigator: sotorasib 960 mg once daily or adagrasib 600 mg twice daily. The registry entry is on ClinicalTrials.gov.
Patients were stratified by history of brain metastases, by which comparator drug was planned, and by KEAP1 mutation status. Patients with active, untreated brain metastases were excluded, and crossover from the control arm to divarasib was not permitted. Median follow-up was 14.3 months.
Roche divarasib Phase 3 trial results: survival and response
- Overall survival: median 17.7 months (95% CI 16.3 to not estimable) versus 12.0 months (95% CI 10.0 to 15.2); hazard ratio 0.56. Twelve-month survival was 67.1% versus 49.2%.
- Progression-free survival by blinded independent review: 9.8 months versus 5.7 months; hazard ratio 0.58 (95% CI 0.44 to 0.76). Twelve-month progression-free survival was 43.9% versus 24.0%.
- Objective response: 58% versus 32%, a difference of 25.8 percentage points. Median duration of response was 11.9 months versus 6.9 months.
Progression-free survival was the primary endpoint. The overall survival result comes from a first interim analysis, so the final survival figures may differ. By our own subtraction, the median survival gap is 5.7 months and the progression-free gap is 4.1 months.
Safety and tolerability in the Roche divarasib Phase 3 trial
The two arms had different side-effect profiles. Grade 3 or 4 treatment-related adverse events occurred in 24.6% of divarasib patients and 34.5% of controls, serious events in 7.8% and 15.2%, and discontinuations because of treatment-related events in 4.8% and 11.7%. No treatment-related deaths occurred in either arm. Median treatment duration was 11.3 months versus 5.0 months.
Gastrointestinal effects were more common with divarasib: diarrhoea in 66% versus 38%, nausea in 53% versus 20% and vomiting in 39% versus 8%. Raised liver enzymes were less common, with ALT elevation in 15% versus 23%. Pneumonitis occurred in three control patients and none on divarasib. Any-grade treatment-related events overall were 92.8% versus 80.1%.
Timeline of the Roche divarasib Phase 3 trial
- 2021 and 2022: sotorasib and adagrasib are cleared by the US FDA, on the basis of tumour response.
- 2025: a single-arm Phase 1 study of divarasib reports a response rate of about 55.6% (per a published summary).
- 2 July 2026: Roche announces that KRASCENDO 1 met its progression-free and overall survival endpoints.
- 25 October 2026: full data presented at ESMO (late-breaking abstract LBA5) and published in the New England Journal of Medicine.
What the investigators and Roche say about the Roche divarasib Phase 3 trial
Roche describes the study as the only global head-to-head trial of a next-generation KRAS G12C inhibitor against approved first-generation drugs, and calls divarasib best-in-class. Ferdinandos Skoulidis of the University of Texas MD Anderson Cancer Center, an investigator, said that based on the results divarasib represents a new standard of care. Those are company and investigator statements, and a regulator has not yet reviewed the data. Roche’s own site is roche.com.
Market context for the Roche divarasib Phase 3 trial
Acumen Research and Consulting’s report Lung Cancer Market Size, Share, Analysis, Trends and Forecast 2022 to 2030 values the global lung cancer market at USD 21.1 billion in 2021 and projects USD 67.9 billion by 2030, a CAGR of 14.1% from 2022 to 2030. The report page was last updated in February 2023, so these are dated estimates and not a measure of KRAS G12C drugs specifically. See more in our Pharmaceutical coverage.
General background: KRAS G12C in lung cancer
KRAS is a gene that, when mutated, can drive tumour growth. The G12C variant occurs in roughly 14% of non-small cell lung cancer cases, according to a trade report. KRAS G12C inhibitors block the mutant protein, and the first approvals were for patients whose disease had progressed after earlier therapy. Divarasib is a next-generation inhibitor designed to bind the target more potently.
Our analysis: a strong signal with open questions
In our assessment, the Roche divarasib Phase 3 trial is the most persuasive evidence so far that a newer KRAS G12C inhibitor can beat the first-generation drugs on survival, and a 44% lower risk of death is large for a previously treated setting. Three cautions apply. The survival data are interim. The trial was open-label, so investigators knew the treatment. And about nine in ten control patients received sotorasib (156 of 171, our calculation), so the result says more about sotorasib than adagrasib.
The higher rate of nausea and vomiting with divarasib is a trade-off against fewer serious events and liver abnormalities, and the net effect for patients will be judged by regulators.
What is not disclosed about the Roche divarasib Phase 3 trial
- Final overall survival and its confidence interval upper bound.
- A regulatory filing date or pricing.
- Survival results in the small adagrasib group.
- Quality-of-life data from the presentation.
Risks and caveats of the Roche divarasib Phase 3 trial
Divarasib is investigational and should not be described as an approved therapy. Results come from the company, the congress presentation and a journal publication as reported, and we have not reviewed the full paper. Acumen market figures are estimates. This article is news reporting and not medical advice; patients should speak to their oncologist.
What to watch next after the Roche divarasib Phase 3 trial
- Regulatory submissions and the first agency decisions.
- Final overall survival analysis.
- KRASCENDO 2, which tests divarasib with pembrolizumab in untreated patients.
- Reactions from the makers of sotorasib and adagrasib.
FAQ
What did the Roche divarasib Phase 3 trial show?
A 44% lower risk of death than sotorasib or adagrasib, with median survival of 17.7 versus 12.0 months.
Is divarasib approved?
No. It is an investigational drug.
Who was in the trial?
338 adults with previously treated, advanced KRAS G12C-mutated non-small cell lung cancer.
How we reported this: we relied on the Roche announcement, the congress presentation and journal publication as reported, the trial registry and the Acumen Research and Consulting report cited above, and attributed every claim. Last updated 26 October 2026. This is news reporting and not advice.