Basel, 2 July 2026. Roche put out an ad hoc announcement, the sort Swiss-listed companies are obliged to issue when news could move the share price, and the news was that divarasib had beaten the lung cancer drugs already on the market. Not a placebo, not chemotherapy. The two approved rivals.
The trial, called Krascendo 1, is a phase III head-to-head in people with previously treated non-small cell lung cancer carrying the KRAS G12C mutation. Roche says it is the only global study to put a KRAS G12C inhibitor directly against the first-generation drugs, sotorasib and adagrasib. It enrolled 338 adults, randomised to take divarasib once a day or a comparator: sotorasib, also daily, or adagrasib, taken twice a day. Progression-free survival, judged by blinded independent central review, was the primary endpoint.
Roche reported that the study met that endpoint and a key secondary one, with improvements in both progression-free survival and overall survival that it called clinically meaningful and statistically significant. The overall survival result arrived at an interim analysis. Safety, the company said, matched earlier data. Side effects were manageable and reversible.
What the first announcement left out
The July statement carried no numbers. They came later. RTTNews, in a report published in late October, gave a hazard ratio for death of 0.56, with a confidence interval of 0.41 to 0.78 and p=0.0005. Put plainly, a 44% cut in mortality risk against the older pair. Median overall survival ran to roughly 18 months on divarasib, against 12 on the control drugs. The objective response rate came close to doubling. Subgroups agreed, whether or not tumours expressed PD-L1 or carried a KEAP1 mutation.
The split was 167 patients on divarasib and 171 on a control inhibitor.
Levi Garraway, who runs global product development as Roche’s chief medical officer, did not hedge. “These results should establish divarasib as a new standard of care for previously-treated lung cancer patients with this genetically defined tumor subtype,” he said.
Why the mutation matters
KRAS G12C turns up in approximately 14% of non-small cell lung cancer cases and is associated with a poor prognosis, which is why Roche describes efficacious treatment as a significant unmet need. Divarasib is an oral, next-generation inhibitor that binds the KRAS G12C protein and locks it in an inactive state, switching off the signalling that drives the tumour. In preclinical work it showed greater potency and selectivity than sotorasib and adagrasib.
The regulatory groundwork is partly laid. In 2022 the US drug regulator, the FDA, gave divarasib Breakthrough Therapy Designation. This year it added an Orphan Drug Designation covering the KRAS G12C form of the disease. The drug remains investigational. Roche said it would present the Krascendo 1 data at a medical meeting and submit them to health authorities, and that it is running further phase III studies of divarasib, alone and in a chemotherapy-free combination.
Sources
- Roche's Divarasib Cuts Death Risk By 44% In Phase 3 KRAS G12C-Mutated Lung Cancer Study (RTTNews)
- Roche: divarasib shows superiority in head-to-head phase III trial (ad hoc announcement)
