Next-generation KRAS drug divarasib beats older pills in lung cancer, extending survival

For non-small-cell lung cancers with the KRAS G12C mutation, two targeted pills, sotorasib and adagrasib, are approved for previously treated patients, but their pivotal trials against chemotherapy did not show — or had not yet reported — longer overall survival, as a Nature Medicine research highlight published on 10 November notes. Roche’s divarasib is designed to be more potent and selective.

The trial

Krascendo 1, published in the New England Journal of Medicine and presented at ESMO 2026, randomised 338 patients with previously treated advanced KRAS G12C-mutated NSCLC to divarasib 400 mg once daily (167) or a first-generation inhibitor (171; 156 got sotorasib, 15 adagrasib).

Results (median follow-up 14.3 months)

• Progression-free survival: 9.8 vs 5.7 months (HR 0.58).
• Overall survival: 17.7 vs 12.0 months (HR 0.56) at the first interim analysis.
• Confirmed response: 58.4% vs 32.3%; median duration of response 11.9 vs 6.9 months.
• Grade 3–4 treatment-related side effects: 24.6% vs 34.5%, even though patients stayed on divarasib about twice as long. Gastrointestinal effects (diarrhoea, nausea, vomiting) were more common with divarasib, mostly low grade.

Limitations

The trial was open-label and funded by Roche, which also makes the drug. The comparison is essentially against sotorasib, with only 15 patients on adagrasib. Overall survival comes from an interim analysis with limited follow-up, people with untreated brain metastases were excluded, and divarasib is still investigational — not yet approved by regulators.