Safety and Efficacy of Durvalumab and Tremelimumab Alone or in Combination in Patients with Advanced Gastric and Gastroesophageal Junction Adenocarcinoma.
Document Type
Article
Publication Date
11-1-2019
Publication Title
Clinical cancer research : an official journal of the American Association for Cancer Research
Abstract
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.
Clinical Institute
Cancer
Clinical Institute
Digestive Health
Department
Oncology
Department
Gastroenterology
Department
Earle A. Chiles Research Institute
Recommended Citation
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.
https://digitalcommons.providence.org/publications/2501
