Multicenter phase Ib/II study of second-line durvalumab and tremelimumab in combination with paclitaxel in patients with biomarker-selected metastatic gastric cancer
Mené sur 7 puis 48 patients atteints d'un cancer de l'estomac de stade métastatique, cet essai multicentrique de phase IB/II détermine les doses maximales tolérées de durvalumab, de trémélimumab et de paclitaxel dispensés en combinaison puis évalue l'efficacité, du point de vue du taux de réponse globale, de cette combinaison en traitement de deuxième ligne et en fonction de spécificités tumorales
Background: This multicenter phase Ib/II trial aimed to evaluate the safety and efficacy of combining durvalumab, tremelimumab, and paclitaxel as second-line treatment for biomarker-selected patients with metastatic gastric cancer.
Methods: In phase Ib, the standard 3 + 3 dose escalation method was used. Durvalumab and tremelimumab were administered every 4 weeks for 13 and 4 cycles, respectively, combining paclitaxel 80 mg/m2 (dose level 2) or 60 mg/m2 (dose level 1) on days 1, 8, and 15. The primary outcome for phase II was the objective response rate (ORR).
Results: In phase Ib (n = 7), dose level-1 was selected as the recommended phase II dose. In phase II, 48 patients were enrolled: microsatellite instability-high or deficient mismatch repair protein tumors (n = 16); EBV-positive tumors (n = 15); high tumor mutation burden ( ≥ 5/Mb) (n = 11); CD274 amplification (n = 5); and POLD1 mutation (n = 1). The ORR was 52.1%, meeting the primary endpoint. The median progression-free survival and overall survival were 5.3 and 13.1 months, respectively. The most common any-grade and grade 3–4 adverse events were anemia (41.7%) and neutropenia (10.4%), respectively.
Conclusions: Durvalumab-tremelimumab with paclitaxel was tolerable and efficacious in biomarker-selected gastric cancer patients as a second-line treatment, highlighting the importance of biomarker-based approaches for immunotherapy in gastric cancer.
British Journal of Cancer , résumé, 2025