Roche's Divarasib Beats Approved KRAS G12C Drugs in Head-to-Head Phase 3 Trial
The Krascendo 1 study met its primary progression-free survival endpoint and showed an overall survival benefit against sotorasib or adagrasib in previously treated KRAS G12C NSCLC, the company said.
These results come from a Phase 3 trial, the large trial usually needed before approval.
Key points
- Roche said on July 2 that divarasib significantly improved progression-free and overall survival compared with sotorasib or adagrasib in the Phase 3 Krascendo 1 trial in previously treated KRAS G12C non-small cell lung cancer.
- The trial enrolled 338 adults; Roche did not release detailed figures and said data will be presented at an upcoming medical meeting and submitted to health authorities.
- A Jefferies analyst called the result a small win and pointed to the first-line Krascendo 2 trial as the larger opportunity, BioPharma Dive reported.
Roche said on July 2 that its investigational KRAS G12C inhibitor divarasib met the primary endpoint of progression-free survival and the key secondary endpoint of overall survival in Krascendo 1, a Phase 3 trial comparing it directly with the approved first-generation drugs sotorasib and adagrasib in patients with previously treated KRAS G12C non-small cell lung cancer (NSCLC), according to the company's announcement. The results are company-reported topline data; Roche did not disclose hazard ratios or median survival figures.
Roche said statistical significance for overall survival was reached at an interim analysis. The safety profile was consistent with previous data, with no new findings, and the most common treatment-related events were manageable and reversible, the company said.
"These results should establish divarasib as a new standard of care for previously-treated lung cancer patients with this genetically defined tumor subtype," said Levi Garraway, Roche's chief medical officer and head of global product development.
The Krascendo 1 trial
Krascendo 1 (NCT06497556) is a randomized, open-label, multicenter Phase 3 study that enrolled 338 adults with previously treated KRAS G12C-mutant advanced or metastatic NSCLC. Patients received once-daily divarasib or the investigator's choice of sotorasib once daily or adagrasib twice daily. The primary endpoint is progression-free survival assessed by blinded independent central review. Roche described it as the only global head-to-head study comparing a KRAS G12C inhibitor with the first-generation drugs.
The comparators are sold by Amgen and Bristol Myers Squibb, BioPharma Dive reported. The G12C mutation occurs in about 14% of NSCLC cases. Divarasib is an oral drug designed to lock the KRAS G12C protein in its inactive state; Roche said it showed greater potency and selectivity than the first-generation drugs in preclinical studies. The FDA granted it breakthrough therapy designation in 2022 and orphan drug designation in 2026.
Market context and next steps
Jefferies analyst Michael Leuchten wrote that the bigger opportunity lies in untreated patients, according to BioPharma Dive. He estimated that success in first-line treatment could open a revenue opportunity of as much as 5 billion Swiss francs, about $6.2 billion, compared with 1 billion to 2 billion francs in the second line. "Krascendo-1 is a small win for Roche, but we view it as premature to claim overall victory," he wrote.
Roche is testing divarasib with Merck's pembrolizumab against pembrolizumab plus chemotherapy in previously untreated patients in the Phase 3 Krascendo 2 trial, and as adjuvant monotherapy after surgery in Krascendo 3. Roche said Krascendo 1 data will be presented at an upcoming medical meeting and submitted to health authorities.
Sources
- Roche's divarasib shows superiority in head-to-head phase III trial against approved KRAS G12C inhibitors in non-small cell lung cancer, Roche, July 2, 2026
- Roche KRAS drug succeeds in head-to-head lung cancer study, BioPharma Dive, July 2, 2026