Roche’s divarasib shows superior survival vs first‑generation KRAS G12C inhibitors in NSCLC
- Divarasib reduced the risk of death by 44% versus sotorasib or adagrasib (OS HR 0.56; 95% CI 0.41–0.78; p=0.0005).
- Median overall survival was 17.7 months with divarasib versus 12.0 months for the control arm.
- Progression‑free survival was 9.8 versus 5.7 months (PFS HR 0.58; 95% CI 0.44–0.76; p<0.0001), a 42% reduction in risk of progression or death.
- Confirmed objective response rate was 58% with divarasib versus 32% with sotorasib/adagrasib; fewer treatment discontinuations and fewer serious TRAEs were reported with divarasib.
Key trial findings
The phase III Krascendo 1 study (NCT06497556), a global randomised head‑to‑head trial of divarasib versus first‑generation KRAS G12C inhibitors, enrolled 338 adults (divarasib n=167; control n=171). Divarasib met primary and key secondary endpoints, showing statistically significant and clinically meaningful improvements in progression‑free survival and overall survival compared with sotorasib or adagrasib.
Efficacy details
Overall survival favored divarasib (median 17.7 months versus 12.0 months; OS HR 0.56, 95% CI 0.41–0.78; p=0.0005). Median PFS was 9.8 months versus 5.7 months (PFS HR 0.58, 95% CI 0.44–0.76; p<0.0001). Confirmed ORR was 58% versus 32%, and benefits were consistent across subgroups including PD‑L1 and KEAP1 status.
Safety and tolerability
No new safety signals were observed; common treatment‑related adverse events were gastrointestinal and hepatotoxicity consistent with class effects. Fewer patients discontinued divarasib for TRAEs (4.8% versus 11.7%), and serious TRAEs were lower (7.8% versus 15.2%) despite longer median treatment duration (11.3 versus 5.0 months).
Regulatory and development status
Data were presented at the 2026 ESMO Congress and published in The New England Journal of Medicine. Divarasib has previously received FDA Breakthrough Therapy designation (2022) and Orphan Drug designation for KRAS G12C‑mutated NSCLC (2026); further phase III studies in first‑line and adjuvant settings are ongoing.
Source: Roche