South San Francisco, California, U.S., October 25, 2026
Genentech, a member of the Roche Group, announced positive Phase 3 results for divarasib, an investigational next-generation KRAS G12C inhibitor, in patients with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC). Findings from the global Krascendo 1 clinical trial demonstrated statistically significant improvements in overall survival and progression-free survival compared with first-generation KRAS G12C inhibitors, sotorasib or adagrasib. Divarasib reduced the risk of death by 44% and the risk of disease progression or death by 42%. Median overall survival reached 17.7 months with divarasib, compared with 12.0 months in the control group. The findings were 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. These results highlight the potential of next-generation targeted therapy to improve outcomes for patients with advanced lung cancer carrying the KRAS G12C mutation.
Divarasib Demonstrates Significant Survival Improvements
The Phase 3 Krascendo 1 study evaluated divarasib monotherapy against sotorasib or adagrasib in adults with previously treated, advanced or metastatic KRAS G12C-mutated NSCLC. The randomized, open-label, multicentre trial enrolled 338 participants, with 167 assigned to divarasib and 171 to the control group. The study met its primary and key secondary endpoints, demonstrating improvements in both progression-free survival and overall survival. Median overall survival was 17.7 months with divarasib versus 12.0 months with the comparator treatments, corresponding to a hazard ratio of 0.56 and a p-value of 0.0005. Median progression-free survival was 9.8 months with divarasib, compared with 5.7 months in the control group, representing a 42% reduction in the risk of progression or death. The 12-month progression-free survival rate was 44% for divarasib and 24% for sotorasib or adagrasib. The reported benefits were consistent across clinically relevant subgroups, including patients with different PD-L1 expression levels and KEAP1 mutation status. These findings suggest that divarasib may provide more durable disease control in this previously treated population.
Higher Tumour Response Rates and Manageable Safety
The study also reported a higher objective response rate with divarasib. The confirmed objective response rate was 58% with divarasib, compared with 32% with sotorasib or adagrasib. Median duration of response reached 11.9 months in the divarasib group, compared with 6.9 months in the control group. These results indicate that more patients experienced measurable tumour shrinkage and that responses lasted longer with the investigational treatment. Genentech reported that the safety profile was consistent with the known effects of KRAS G12C inhibitors, with no new safety signals identified. The most common treatment-related adverse events included gastrointestinal effects, particularly diarrhoea, nausea and vomiting, as well as liver-related toxicity. Treatment discontinuations due to treatment-related adverse events occurred in 4.8% of patients receiving divarasib, compared with 11.7% in the control group. Serious treatment-related adverse events were reported in 7.8% of the divarasib group and 15.2% of patients receiving sotorasib or adagrasib. These findings are relevant when assessing the overall benefit-risk profile, although ongoing clinical and regulatory evaluation will be needed before divarasib can become an approved treatment option.
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Genentech Advances KRAS-Targeted Lung Cancer Research
Divarasib is an investigational oral therapy designed to selectively inhibit the KRAS G12C protein, a mutated protein involved in tumour-driving cellular growth signals. The G12C mutation can keep the KRAS signalling pathway abnormally active, promoting cancer-cell proliferation. Divarasib is designed to bind selectively to the mutated protein and lock it in an inactive state, interrupting these signals. KRAS G12C mutations are found in approximately 12–14% of NSCLC cases, creating a defined population for targeted treatment research. Despite the availability of first-generation KRAS G12C inhibitors, patients whose disease progresses after earlier treatment continue to need additional options. Genentech is advancing a broader Phase 3 development programme for divarasib, including Krascendo 2, which evaluates divarasib plus pembrolizumab in previously untreated advanced NSCLC, and Krascendo 3, which investigates adjuvant divarasib after surgery and standard chemoimmunotherapy. The U.S. Food and Drug Administration granted divarasib Breakthrough Therapy Designation in 2022 and Orphan Drug Designation for KRAS G12C-mutated NSCLC in 2026. Divarasib remains investigational and is not yet approved for routine clinical use. Further regulatory review and clinical development will determine its future role in lung cancer treatment.
Source: Genentech press release
