Roche has announced results from the phase 3 Krascendo 1 study. The study compared investigational divarasib, a next-generation KRAS G12C inhibitor, with current standard of care KRAS G12C inhibitors in people with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Participants treated with divarasib monotherapy lived significantly longer, lowering the risk of death by 44% compared with sotorasib or adagrasib. Median OS for divarasib is currently approximately 18 months, compared to 12 months for the control arm. No new safety findings were observed with divarasib and the most common treatment-related adverse events (TRAEs) were mainly low grade and manageable.
The data was presented as a late-breaking abstract during a Presidential Symposium at the 2026 European Society for Medical Oncology (ESMO) Congress and simultaneously published in The New England Journal of Medicine.
Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development, said: “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, found in approximately one in eight people with NSCLC. Accumulating evidence suggests that people with NSCLC who have the KRAS G12C mutation may have poorer outcomes than those who have the unmutated KRAS gene (wild-type disease). Despite the approval of current, first-generation KRAS G12C-targeted treatments, there remains a significant unmet need for more effective therapy options.
“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,” said study lead author Ferdinandos Skoulidis, Professor of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center.
The Krascendo 1 study is the only global head-to-head study to evaluate a next-generation KRAS G12C inhibitor versus approved first-generation KRAS G12C inhibitors.
Roche is advancing a comprehensive phase III clinical development programme in NSCLC, investigating divarasib as both a monotherapy and as a chemotherapy-free combination, across different disease settings and lines of therapy. The US Food and Drug Administration granted Breakthrough Therapy Designation to divarasib in 2022, and in 2026, Orphan Drug Designation for KRAS G12C-mutated NSCLC.