Headline numbers from a Phase 3 trial are easy to quote and harder to interpret. The Roche divarasib Phase 3 trial, KRASCENDO 1, reported a 44% lower risk of death in previously treated KRAS G12C-mutated non-small cell lung cancer, but the design details decide how far that result can be pushed. This article walks through who was enrolled, what the comparison drugs were and which parts of the data are still preliminary. Divarasib is investigational and is not an approved therapy.
Key takeaways: reading the Roche divarasib Phase 3 trial
- 338 patients were randomised in an open-label trial; crossover was not allowed.
- Control patients received sotorasib (156 patients) or adagrasib (15 patients) at the investigator’s choice.
- Overall survival hazard ratio 0.56 at a first interim analysis; median 17.7 versus 12.0 months.
- Primary endpoint, progression-free survival, was 9.8 versus 5.7 months (hazard ratio 0.58).
- Response rate was 58% versus 32%, and grade 3 or 4 treatment-related events were 24.6% versus 34.5%.
The patient population in the Roche divarasib Phase 3 trial
Participants were adults with locally advanced or metastatic non-small cell lung cancer carrying the KRAS G12C mutation, all of whom had received earlier treatment. Patients with active, untreated brain metastases were excluded, and about 29% to 30% in each arm had a history of brain metastases. Randomisation was stratified by brain metastasis history, by the planned comparator and by KEAP1 mutation status, a marker associated with poorer outcomes. The registry record is at ClinicalTrials.gov.
Median follow-up was 14.3 months. The trial was sponsored by Roche, and the full results were presented at the ESMO 2026 congress and published in the New England Journal of Medicine.
The comparison treatments in the Roche divarasib Phase 3 trial
The control arm used approved first-generation KRAS G12C inhibitors. Sotorasib is taken once daily at 960 mg and adagrasib twice daily at 600 mg. According to a trade report, both were cleared by the US FDA on the basis of tumour response and not of a proven survival benefit, with sotorasib carrying warnings for liver injury and lung inflammation and adagrasib for QT prolongation and drug interactions.
Because 156 of the 171 control patients took sotorasib, which is about 91% by our own calculation, the control arm is mainly a sotorasib comparison. The trial was not designed to compare divarasib separately with each drug, and the adagrasib group is too small to analyse on its own.
How the Roche divarasib Phase 3 trial measured benefit
- Progression-free survival by blinded independent central review was the primary endpoint: 9.8 months (95% CI 8.1 to 12.9) versus 5.7 months (95% CI 4.2 to 6.8).
- Overall survival was a secondary endpoint, analysed at a first interim: 17.7 months (95% CI 16.3 to not estimable) versus 12.0 months (95% CI 10.0 to 15.2).
- Confirmed response: 58% versus 32%; median duration of response 11.9 versus 6.9 months.
Blinded independent review of progression reduces the bias of an open-label design, but overall survival is not subject to that bias at all, which is why the survival result carries weight. The upper end of the survival interval is not yet estimable, which signals immature data.
Subgroups worth noting in the Roche divarasib Phase 3 trial
In patients with KEAP1 mutations, median progression-free survival was 4.6 months versus 2.8 months (hazard ratio 0.56), a smaller absolute gain in a harder-to-treat group. In patients with a history of brain metastases it was 6.8 versus 5.7 months (hazard ratio 0.74, with an interval that crosses 1), so the benefit there is less certain. These subgroup analyses involve small numbers and are not designed to prove anything on their own.
Safety in the Roche divarasib Phase 3 trial
Median treatment duration was 11.3 months on divarasib and 5.0 months on control, so divarasib patients were exposed for longer. Serious treatment-related events were 7.8% versus 15.2% and discontinuations 4.8% versus 11.7%. Diarrhoea, nausea and vomiting were more frequent with divarasib, at 66%, 53% and 39%, against 38%, 20% and 8% with controls. No treatment-related QT prolongation or pneumonitis was reported with divarasib, while two and three control patients had those events respectively.
Market context by region
Acumen Research and Consulting’s report Lung Cancer Market Size, Share, Analysis, Trends and Forecast 2022 to 2030 says North America held more than 35.5% of the global lung cancer market in 2021 and that Asia Pacific is expected to show the fastest growth. It states that non-small cell lung cancer accounted for more than 60% of the market in 2021 and about 84% of lung cancer cases. The page was last updated in February 2023, so the figures are dated and do not break out KRAS G12C therapies. More in our Pharmaceutical section.
General background: why head-to-head data matter
Most cancer drugs are approved on trials against chemotherapy or placebo. A head-to-head comparison with an approved drug of the same class answers the question doctors actually face, which is which option to choose. That is why Roche emphasises that KRASCENDO 1 is the only global head-to-head trial of a next-generation KRAS G12C inhibitor against approved drugs.
Our analysis of the Roche divarasib Phase 3 trial
In our assessment, the Roche divarasib Phase 3 trial is persuasive because progression-free survival, response and survival all point the same way, and the control arm used approved drugs. The main limits are the interim survival data, the open-label design and the near absence of an adagrasib comparison. We do not predict regulatory outcomes.
Investigators and the company describe divarasib as a new standard of care. That is their characterisation and not a regulatory decision.
What is not disclosed about the Roche divarasib Phase 3 trial
- Final overall survival and its confidence interval.
- Regulatory filing plans.
- Quality-of-life outcomes.
- Outcomes for the adagrasib subgroup.
Risks and caveats of the Roche divarasib Phase 3 trial
The figures are as presented and published, as reported to us, and we have not reviewed the full paper. Divarasib is investigational. Acumen market numbers are third-party estimates. This is news reporting and not medical advice.
What to watch next after the Roche divarasib Phase 3 trial
- Regulatory filings and decisions.
- Final survival analysis.
- Results from KRASCENDO 2 and KRASCENDO 3.
- Safety updates with longer follow-up.
FAQ
Was the Roche divarasib Phase 3 trial blinded?
No. It was open-label, although progression was assessed by blinded independent review.
Which drugs did divarasib beat?
Sotorasib in most control patients and adagrasib in a few.
Is divarasib available?
No. It is investigational.
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.
