SHERIDAN, WYOMING -- July 07, 2026 -- Roche announced positive results from the phase III Krascendo 1 study, showing that its investigational KRAS G12C inhibitor divarasib outperformed the approved first-generation inhibitors sotorasib and adagrasib in patients with previously treated KRAS G12C non-small cell lung cancer. The study met both its primary and key secondary endpoints, with divarasib delivering statistically significant improvements in progression-free survival and overall survival. Roche plans to submit the data to health authorities and present full results at an upcoming medical meeting. The company positions the results as evidence that divarasib could become a new treatment standard for this genetically defined subgroup of lung cancer patients.
Krascendo 1 Delivers the First Global Head-to-Head Comparison
Krascendo 1 is the only global study to directly compare a KRAS G12C inhibitor against first-generation drugs already approved for the same mutation. The randomized, open-label trial enrolled 338 adults with previously treated, advanced or metastatic KRAS G12C-mutant non-small cell lung cancer. Participants received either divarasib once daily or one of the approved comparators, sotorasib once daily or adagrasib twice daily. Blinded independent central review of progression-free survival served as the primary endpoint, with overall survival, response rate and duration of response tracked as secondary measures.
Survival Data Reach Statistical Significance Early
Overall survival results reached statistical significance at an interim analysis, a notable finding given the poor prognosis typically associated with this patient population. Progression-free survival improvements were described as clinically meaningful alongside the survival benefit. Roche reported no new safety signals in the trial. Treatment-related side effects were consistent with divarasib's existing safety profile and were largely manageable and reversible, according to the company.
Roche's Chief Medical Officer Frames the Data as Practice-Changing
"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, Roche's Chief Medical Officer and Head of Global Product Development.
Garraway added that the results should establish divarasib as a new standard of care for previously treated lung cancer patients carrying this specific tumor mutation.
KRAS G12C Remains a High-Burden, Underserved Mutation
The KRAS G12C mutation appears in roughly 14% of non-small cell lung cancer cases and is linked to worse patient outcomes. KRAS mutations overall occur in about a quarter of newly diagnosed lung cancers, making the gene one of the most frequently altered targets in the disease. Lung cancer causes an estimated 1.8 million deaths each year worldwide, with non-small cell disease accounting for roughly 85% of cases. Treatment options for this specific mutation subtype have lagged behind the broader lung cancer field, leaving a gap Roche is targeting with divarasib.
A Three-Study Program Spans Early to Late-Stage Disease
Roche is running divarasib through three phase III studies covering different points in the treatment pathway. Krascendo 1 tests divarasib monotherapy against approved inhibitors in previously treated, second-line patients. Krascendo 2 pairs divarasib with pembrolizumab as a chemotherapy-free combination for untreated, first-line patients, comparing it against chemotherapy plus pembrolizumab. Krascendo 3 evaluates adjuvant divarasib monotherapy against immunotherapy or observation in resected early-stage disease following standard chemoimmunotherapy. The U.S. Food and Drug Administration granted divarasib Breakthrough Therapy Designation in 2022 and Orphan Drug Designation for KRAS G12C non-small cell lung cancer in 2026.
Divarasib Builds on Roche's Existing Lung Cancer Portfolio
Divarasib is designed to bind selectively to the mutated KRAS G12C protein, locking it in an inactive state and shutting down the signaling that drives tumor growth. Preclinical work showed greater potency and selectivity for divarasib compared with sotorasib and adagrasib. The drug extends a lung cancer portfolio that already includes Roche's approved medicines Alecensa, Tecentriq and Rozlytrek. Roche says its broader pipeline spans small cell lung cancer and both genomically defined and non-defined subtypes of non-small cell disease.