Roche has released results from the phase 3 Krascendo 1 study, comparing the investigational drug divarasib with current KRAS G12C inhibitors in patients with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC).
The study found that participants treated with divarasib monotherapy lived significantly longer, reducing the risk of death by 44% compared to those on sotorasib or adagrasib. The median overall survival (OS) for divarasib is approximately 18 months, versus 12 months for the control group. No new safety concerns were identified, with most treatment-related adverse events (TRAEs) being low-grade and manageable.
The findings were presented at the 2026 European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine.
Levi Garraway, Roche’s Chief Medical Officer, stated, The phase 3 Krascendo 1 results demonstrate the potential for divarasib to become a new standard of care for people with previously treated KRAS G12C-mutated lung cancer. The superior efficacy against the current standard of care demonstrated in this head-to-head trial reinforces divarasib’s best-in-class profile.
The G12C mutation is one of the most common KRAS mutations, occurring in about one in eight NSCLC patients. Evidence suggests that individuals with this mutation may have poorer outcomes compared to those with the unmutated KRAS gene. Despite the approval of first-generation treatments, there remains a significant need for more effective therapies.
New treatments have previously extended survival for patients with specific genetic mutations. In recent years, targeted therapies have transformed outcomes for certain cancer types, offering hope where previously few options existed.
Ferdinandos Skoulidis, the study’s lead author, noted, New life-extending treatments are greatly needed, as most patients with this type of cancer will eventually relapse after initial therapy, and there are limited effective treatments for recurrent disease.
Krascendo 1 is the only global head-to-head study evaluating a next-generation KRAS G12C inhibitor against approved first-generation inhibitors. Roche is advancing a phase III clinical development program for NSCLC, testing divarasib as both a monotherapy and in chemotherapy-free combinations across various disease settings.
The US Food and Drug Administration granted Breakthrough Therapy Designation to divarasib in 2022 and Orphan Drug Designation for KRAS G12C-mutated NSCLC in 2026.
