Roche's Divarasib Beats Approved KRAS G12C Drugs Head-to-Head in Phase 3 Lung Cancer Trial
Roche says its next-generation inhibitor divarasib improved both progression-free and overall survival versus approved KRAS G12C drugs in a 338-patient Phase 3 NSCLC trial.
Overview
Roche announced on 2 July 2026 that its investigational drug divarasib beat two already-approved KRAS G12C inhibitors in a head-to-head Phase 3 lung cancer trial, according to the company’s press release. In the Krascendo 1 study, divarasib “met its primary and key secondary endpoint, with divarasib achieving clinically meaningful and statistically significant improvements in both progression-free survival (PFS) and overall survival (OS),” Roche said in its ad hoc announcement.
The result is notable because it is a direct comparison between a next-generation drug and the first-generation KRAS G12C inhibitors already on the market, rather than the more common comparison against chemotherapy.
What We Know
Krascendo 1 (NCT06497556) is a global, randomized, open-label Phase 3 trial in patients with previously treated advanced or metastatic KRAS G12C-mutant non-small cell lung cancer (NSCLC), according to OncoDaily. The study enrolled 338 adults and compared once-daily divarasib with either once-daily sotorasib or twice-daily adagrasib, both of which are approved, first-generation KRAS G12C inhibitors, according to Roche.
The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival, with key secondary endpoints including overall survival, confirmed objective response, and duration of response, according to OncoDaily. Roche reported that no new safety signals were observed, according to its ad hoc announcement.
Divarasib is an oral small molecule that, like other covalent KRAS G12C inhibitors, is designed to bind the mutant KRAS protein and lock it in an inactive state, according to OncoDaily. In the Krascendo 1 trial, patients had disease that had progressed after at least one but no more than three prior lines of systemic therapy, and the two comparator arms used Amgen’s Lumakras (sotorasib) and BMS’s Krazati (adagrasib), according to MedCity News.
The drug previously received Breakthrough Therapy Designation from the U.S. Food and Drug Administration in 2022 and Orphan Drug Designation for KRAS G12C NSCLC in 2026, according to Roche.
“The superior survival demonstrated in this global head-to-head comparison of KRAS G12C inhibitors confirms the potential of divarasib to improve clinical outcomes for people with KRAS G12C non-small cell lung cancer,” said Levi Garraway, MD, PhD, Chief Medical Officer and Head of Global Product Development at Roche, according to the company’s press release.
What We Don’t Know
Roche has not yet disclosed median survival outcomes, hazard ratios, response rates, subgroup analyses, or full safety data, according to OncoDaily. The magnitude of the progression-free and overall survival benefit therefore remains unquantified in the public topline. Roche said the full data will be presented at an upcoming medical meeting and submitted to health authorities, according to its press release. Regulatory timelines and potential approval decisions have not been announced.
Analysis
KRAS was long considered an “undruggable” cancer target, and the first-generation inhibitors sotorasib and adagrasib established that the mutation could be drugged at all. A head-to-head Phase 3 win against those incumbents, rather than against chemotherapy, is a more demanding bar: Roche positions divarasib as a next-generation inhibitor designed to offer greater potency and selectivity compared with the Amgen and BMS products, according to MedCity News. If the detailed data hold up at a medical meeting, the result would reframe the KRAS G12C market around comparative survival benefit rather than mechanism-of-action novelty. Until the underlying numbers are released, however, the size of divarasib’s advantage cannot be assessed.