Efficacy and safety of garsorasib in patients with KRAS G12C-mutated advanced pancreatic cancer
Menée à partir de données de deux essais internationaux de phase I/II incluant 24 patients atteints d'un cancer du pancréas de stade avancé avec mutation G12C au niveau du gène KRAS (durée médiane de suivi : 8,9 mois), cette étude évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du garsorasib (un inhibiteur de KRASG12C dispensé par voie orale)
Background: Garsorasib (D-1553), a highly selective, oral KRASG12C inhibitor, has shown clinical efficacy in NSCLC and CRC and is under evaluation in pancreatic cancer.
Methods: Pancreatic cancer patients with KRAS G12C mutation were enroled and received garsorasib 600 mg twice daily treatment in two international, multicenter, open-label phase 1/2 trials (NCT04585035 and NCT05383898) with similar eligibility criteria. Their data were pooled for analyses of efficacy and safety endpoints.
Results: As of April 30, 2024, 24 KRAS G12C–mutated pancreatic cancer patients were enroled with a median follow-up of 8.9 months (range 1.1–22.9). Among 22 evaluable patients, the confirmed objective response rate (ORR) was 45.5% (95% CI, 24.4 to 67.8) with a median duration of response (DOR) of 6.4 months (95% CI, 4.2 to 16.4). The median progression-free survival (PFS) was 7.6 months (95% CI, 3.3 to 8.5) and the 6-month OS rate was 79.2% (95% CI, 57.0, 90.8). Treatment-related adverse events (TRAEs) occurred in 18 (75.0%) patients, including 6 (25.0%) with grade ≥3 events. No TRAEs led to treatment discontinuation. The safety profile was consistent with previous reports of garsorasib.
Conclusion: Garsorasib demonstrated encouraging antitumor activity and a tolerable safety profile in patients with KRAS G12C-mutated advanced pancreatic cancer.
British Journal of Cancer , résumé, 2025