British journal of cancer · 2025
Multicenter phase Ib/II study of second-line durvalumab and tremelimumab in combination with paclitaxel in patients with biomarker-selected metastatic gastric cancer.
СтатьяКлиническое исследование II фазыМногоцентровое исследованиеКлиническое исследование I фазыНазвание и аннотация: Перевод пока не подготовлен
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Lee Keun-Wook, Zang Dae Young, Kim Hyung-Don, Kim Jin-Won, Kim Bum Jun, Kang Yoon-Koo, Ryu Min-Hee, Kim Hark Kyun
Аннотация
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.
CLINICAL TRIAL REGISTRATION: NCT03751761.
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.
CLINICAL TRIAL REGISTRATION: NCT03751761.