• Ronan J Kelly, Jeeyun Lee, Yung-Jue Bang, Khaldoun Almhanna, Mariela Blum-Murphy, Catenacci Daniel V T DVT Department of Medicine, Division of Hematology-Oncology, The University of Chicago Medicine Comprehensive Cancer Center, Chicago, Illinois., Hyun Cheol Chung, Zev A Wainberg, Michael K Gibson, Keun-Wook Lee, Johanna C Bendell, Crystal S Denlinger, Cheng Ean Chee, Takeshi Omori, Rom Leidner, Heinz-Josef Lenz, Yee Chao, Marlon C Rebelatto, Philip Z Brohawn, Peng He, Jennifer McDevitt, Siddharth Sheth, Judson M Englert, and Geoffrey Y Ku.
• The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Ronan.Kelly@BSWHealth.org.
• Clin Cancer Res. 2020 Feb 15; 26 (4): 846-854.

PurposeThis randomized, multicenter, open-label, phase Ib/II study assessed durvalumab and tremelimumab in combination or as monotherapy for chemotherapy-refractory gastric cancer or gastroesophageal junction (GEJ) cancer.Patients And MethodsSecond-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 IFNγ 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 (PFS) rate at 6 months.ResultsA total of 113 patients were treated: 6 in phase Ib and 107 (arm A, 27; arm B, 24; arm C, 12; arm D, 25; arm E, 19) in phase II. Overall response rates were 7.4%, 0%, 8.3%, 4.0%, and 15.8% in the five arms, respectively. PFS 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.ConclusionsResponse rates were low regardless of monotherapy or combination strategies. No new safety signals were identified. Including use of a tumor-based IFNγ 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.©2019 American Association for Cancer Research.

36 keywords...

hide…