What does the Roche divarasib Phase 3 trial mean for the KRAS G12C market? Roche’s KRASCENDO 1 study showed a 44% lower risk of death than sotorasib or adagrasib in previously treated lung cancer, with median survival of 17.7 months against 12.0 months. For Amgen, whose Lumakras was first to market, and Bristol Myers Squibb, which owns Krazati, it is a direct challenge. Divarasib is investigational and has not been approved by any regulator.
Key takeaways: the Roche divarasib Phase 3 trial and competition
- The trial randomised 338 patients; overall survival hazard ratio was 0.56 at a first interim analysis.
- Response rate was 58% versus 32%, and progression-free survival was 9.8 versus 5.7 months.
- Control patients took Amgen’s sotorasib (156 patients) or Bristol Myers Squibb’s adagrasib (15 patients).
- A Jefferies analyst has said the larger commercial prize is in untreated patients and depends on a separate trial.
- No filing timeline or price has been disclosed.
What the Roche divarasib Phase 3 trial tested
KRASCENDO 1 (NCT06497556) is a global, open-label, randomised trial of divarasib 400 mg once daily versus an approved KRAS G12C inhibitor in adults with previously treated, locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer. Progression-free survival by blinded independent review was the primary endpoint, at 9.8 months versus 5.7 months (hazard ratio 0.58). Median follow-up was 14.3 months, and crossover was not allowed. The trial record is on ClinicalTrials.gov.
The numbers that matter commercially in the Roche divarasib Phase 3 trial
- Overall survival: 17.7 months versus 12.0 months (hazard ratio 0.56; 95% CI 0.41 to 0.78). Twelve-month survival 67.1% versus 49.2%.
- Confirmed response rate: 58% versus 32%, with response lasting a median of 11.9 versus 6.9 months.
- Median treatment duration: 11.3 versus 5.0 months, which matters because oral cancer drugs are paid for by the month.
- Serious treatment-related events: 7.8% versus 15.2%; discontinuations 4.8% versus 11.7%.
Nausea, vomiting and diarrhoea were more frequent with divarasib (53%, 39% and 66% against 20%, 8% and 38%), which prescribers will weigh against the lower rates of serious events and liver abnormalities.
Competitive landscape for the Roche divarasib Phase 3 trial
Sotorasib was the first KRAS-targeting drug approved, in 2021, and adagrasib followed in 2022. Bristol Myers Squibb acquired adagrasib’s developer Mirati Therapeutics in 2023 for USD 4.8 billion, according to a trade report. Both drugs were cleared on the basis of tumour response and not survival, which is why a Phase 3 survival advantage for a new entrant is notable.
The comparison has a limit for adagrasib’s owner: only 15 control patients received it, so the trial says little about divarasib versus Krazati specifically. That is our reading of the reported numbers.
Analyst view of the Roche divarasib Phase 3 trial and the untreated-patient opportunity
After Roche’s July announcement that the trial was positive, Jefferies analyst Michael Leuchten described KRASCENDO 1 as a small win for Roche and said it was premature to claim overall victory. He estimated the opportunity in previously treated patients at CHF 1 billion to 2 billion and the opportunity in untreated patients at up to CHF 5 billion, a figure that depends on KRASCENDO 2, which tests divarasib with Merck’s pembrolizumab against pembrolizumab plus chemotherapy. These are an analyst’s estimates, not company guidance, and were made before the full data were presented.
Timeline of the Roche divarasib Phase 3 trial
- 2021 and 2022: first-generation KRAS G12C inhibitors cleared by the US FDA.
- 2 July 2026: Roche announces KRASCENDO 1 met its survival endpoints.
- 25 October 2026: full data at ESMO 2026 and in the New England Journal of Medicine.
- 26 October 2026: KRASCENDO 3 trial-in-progress poster, testing divarasib after surgery in earlier-stage disease.
Lung cancer market data and 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% for 2022 to 2030. It says non-small cell lung cancer held more than 60% of the market in 2021 and lists targeted therapies for EGFR, ALK, ROS-1, NTRK, MET, RET and BRAF V600E among the approved options. The page was last updated in February 2023 and does not discuss KRAS G12C separately, so the figures are dated context. More in our pharmaceuticals coverage.
General background: why second line first
Drugs are often tested first in patients whose cancer has progressed after earlier treatment, because the benefit is easier to demonstrate and the regulatory path is clear. A win there lets a company argue for earlier use. Roche’s planned trials in untreated and earlier-stage patients are the route to a bigger market.
Our analysis of the Roche divarasib Phase 3 trial: commercial implications
In our assessment, the Roche divarasib Phase 3 trial strengthens Roche’s hand because it shows survival benefit against drugs that were not approved on survival. Commercially, the key questions are regulatory timing, pricing against two established brands and the untreated-patient data. A tolerability profile with more gastrointestinal effects could affect how patients stay on therapy, although longer treatment duration on divarasib suggests many did.
We do not forecast sales and do not give investment advice.
What is not disclosed about the Roche divarasib Phase 3 trial
- Filing dates, label scope and price.
- Final overall survival.
- Peak-sales estimates from the company.
- Responses from the other manufacturers.
Risks and caveats
Divarasib is an investigational drug and must not be described as approved. Analyst estimates are opinion. The survival data are interim. Acumen figures are third-party estimates for the whole lung cancer market. This article is news reporting and not investment or medical advice.
What to watch next after the Roche divarasib Phase 3 trial
- First regulatory filings by Roche.
- KRASCENDO 2 results in untreated patients.
- Competitor data updates from sotorasib and adagrasib makers.
- Final overall survival analysis.
FAQ
Who are Roche’s competitors after the Roche divarasib Phase 3 trial?
Amgen’s sotorasib and Bristol Myers Squibb’s adagrasib are the approved KRAS G12C drugs it was compared with.
Is divarasib approved?
No. It remains investigational.
What is the bigger opportunity?
An analyst estimates it lies in untreated patients and depends on a separate trial.
How we reported this: we relied on the Roche announcement, the congress presentation and journal publication as reported, an analyst note 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.
