• Divarasib monotherapy demonstrated superior efficacy over first-generation KRAS G12C inhibitors, lowering the risk of disease progression or death by 42% and the overall risk of death by 44%, in the phase III Krascendo 1 study^1,2
• At the time of primary analysis, divarasib achieved a median overall survival of approximately 18 months, compared to 12 months for sotorasib or adagrasib^1,2
• No new safety signals were observed with divarasib; the most common treatment-related adverse events were mainly low grade and manageable^1,2
• Data presented as a late-breaking abstract during a Presidential Symposium at the 2026 ESMO Congress and simultaneously published in The New England Journal of Medicine^1,2

Roche (SIX: RO, ROP; OTCQX: RHHBY) announced pivotal results from the phase III Krascendo 1 study, which demonstrated the superior efficacy of investigational divarasib, a next-generation KRAS G12C inhibitor, compared with current standard of care KRAS G12C inhibitors in people with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC).^1,2 Participants treated with divarasib monotherapy lived significantly longer, lowering the risk of death by 44% compared with sotorasib or adagrasib (overall survival, OS, HR 0.56, [95% CI: 0.41-0.78], p=0.0005).^1,2 Median OS for divarasib is currently approximately 18 months, compared to 12 months for the control arm (see table below).^1,2 No new safety findings were observed with divarasib and the most common treatment-related adverse events (TRAEs) were mainly low grade and manageable.^1,2 These data 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.^1,2

“The phase III 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,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. "The superior efficacy against the current standard of care demonstrated in this head-to-head trial reinforces divarasib's best-in-class profile. We are working closely with health authorities to bring this new treatment option to the people who need it.”

The G12C mutation is one of the most common KRAS mutations, found in approximately one in eight people with NSCLC.^3,4 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).^5,6 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, MD, PhD, Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “The Krascendo 1 results highlight divarasib’s practice-changing potential, as the first KRAS inhibitor to meaningfully improve overall survival for people with previously treated KRAS G12C-mutated lung cancer, compared with current treatment options.”

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.^1,2 The study met primary and key secondary endpoints, and divarasib demonstrated statistically significant and clinically meaningful improvements in OS and progression-free survival (PFS) over sotorasib or adagrasib.^1,2 In addition to the OS benefit, divarasib reduced the risk of disease progression or death by 42% (PFS HR 0.58, [95% CI: 0.44-0.76], p<0.0001).^1,2 The OS and PFS benefit was consistent across clinically relevant subgroups, and was observed regardless of PD-L1 expression or KEAP1 mutation status.^1,2 The objective response rate (ORR) with divarasib was nearly double that of sotorasib or adagrasib.^1,2

Key efficacy results from the phase III Krascendo 1 study:^1,2

*Assessed in response-evaluable population (n=328; ten patients [divarasib arm, n=6; control arm, n=4] did not have measurable disease at baseline and were excluded from the response-evaluable set). Duration of Response (DOR) evaluated in those who responded to treatment (divarasib arm, n=94; control arm, n=54).

The safety profile of divarasib monotherapy was consistent with the known class effects of KRAS G12C inhibitors.^1,2 The most common TRAEs comprised GI toxicity (most commonly, diarrhoea, nausea, and vomiting) and hepatotoxicity.^1,2 Fewer participants discontinued treatment due to TRAEs with divarasib (4.8% versus 11.7%) and the rate of serious TRAEs was approximately half that of sotorasib or adagrasib (7.8% versus 15.2% respectively), despite patients remaining on treatment for more than twice as long (11.3 months compared with 5.0 months).^1,2

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.