Safety and Efficacy of Durvalumab and Tremelimumab Alone or in Combination in Patients with Advanced Gastric and Gastroesophageal Junction Adenocarcinoma.
Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE: This randomized, multicenter, open-label, phase 1b/2 study assessed durvalumab and tremelimumab in combination or as monotherapy for chemotherapy-refractory gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.
EXPERIMENTAL DESIGN: Second-line patients were randomized 2:2:1 to receive durvalumab plus tremelimumab (arm A), or durvalumab (arm B) or tremelimumab monotherapy (arm C), and third-line patients received durvalumab plus tremelimumab (arm D). A tumor-based interferon-gamma gene signature was prospectively evaluated as a potential predictive biomarker in second- and third-line patients receiving the combination (arm E). The coprimary endpoints were objective response rate and progression-free survival rate at 6 months.
RESULTS: A total of 113 patients were treated: 6 in phase 1b and 107 (arm A, 27; arm B, 24; arm C, 12; arm D, 25; arm E, 19) in phase 2. Overall response rates were 7.4%, 0%, 8.3%, 4.0%, and 15.8% in the five arms, respectively. Progression-free survival rates at 6 months were 6.1%, 0%, 20%, 15%, and 0%, and 12-month overall survival rates were 37.0%, 4.6%, 22.9%, 38.8%, and NA, respectively. Treatment-related grade 3/4 adverse events were reported in 17%, 4%, 42%, 16%, and 11% of patients, respectively.
CONCLUSIONS: Response rates were low regardless of monotherapy or combination strategies. No new safety signals were identified. Including use of a tumor-based interferon-γ signature and change in baseline and on-treatment circulating tumor DNA are clinically feasible and may be novel strategies to improve treatment response in this difficult-to-treat population.
Earle A. Chiles Research Institute
Kelly, Ronan J; Lee, Jeeyun; Bang, Yung-Jue; Almhanna, Khaldoun; Blum Murphy, Mariela; Catenacci, Daniel V T; Chung, Hyun Cheol; Wainberg, Zev A; Gibson, Michael K; Lee, Keun-Wook; Bendell, Johanna C; Denlinger, Crystal S; Chee, Cheng Ean; Omori, Takeshi; Leidner, Rom; Lenz, Heinz-Josef; Chao, Yee; Rebelatto, Marlon C; Brohawn, Philip; He, Peng; McDevitt, Jennifer; Sheth, Siddharth; Englert, Judson M; and Ku, Geoffrey Y, "Safety and Efficacy of Durvalumab and Tremelimumab Alone or in Combination in Patients with Advanced Gastric and Gastroesophageal Junction Adenocarcinoma." (2019). Articles, Abstracts, and Reports. 2501.