Design: Phase 3, international, open-label randomised trial (Krascendo 1)
Population: 338 patients with previously treated KRAS G12C-mutated advanced NSCLC
Primary outcome: Progression-free survival by blinded independent review
Effect: PFS 9.8 vs 5.7 months, HR 0.58 (0.44 to 0.76); OS 17.7 vs 12.0 months, HR 0.56

Krascendo 1 was an open-label phase 3 trial in 338 patients with previously treated KRAS G12C-mutated advanced non-small-cell lung cancer. They received divarasib or a first-generation KRAS G12C inhibitor, mostly sotorasib.

Median progression-free survival, by blinded central review, was 9.8 months with divarasib and 5.7 months with control (hazard ratio 0.58, 95% CI 0.44 to 0.76). Median overall survival was 17.7 against 12.0 months (0.56, 0.41 to 0.78). Responses were 58.4% against 32.3%, and grade 3–4 treatment-related adverse events were less frequent (24.6% against 34.5%).

A head-to-head win on both efficacy and tolerability is uncommon. If approved, divarasib would likely displace first-generation agents in this setting. Its regulatory status in India and elsewhere is not established by this paper, and the trial was sponsored by the manufacturer.

Test for KRAS G12C in advanced non-squamous NSCLC as part of molecular profiling.
Note that divarasib outperformed first-generation G12C inhibitors on survival and tolerability.
Check regulatory approval and access before planning sequencing around divarasib.
Expect most control patients in this trial to have received sotorasib.

Why it matters

It is a rare direct comparison showing a newer drug in the same class is better, not just different.

The statistics, in plain English

A hazard ratio for death of 0.56 means about 44% lower risk of dying at any point. Median survival gains of about six months are large in this setting. Open-label design matters less here because progression was assessed by blinded central review.