Safety and efficacy of durvalumab and tremelimumab alone or in combination in patients with advanced gastric and gastroesophageal junction adenocarcinoma

Ronan J. Kelly, Jeeyun Lee, Yung Jue Bang, Khaldoun Almhanna, Mariela Blum-Murphy, Daniel V.T. Catenacci, 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 HeJennifer McDevitt, Siddharth Sheth, Judson M. Englert, Geoffrey Y. Ku

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76 Citations (Scopus)


Purpose: This 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 Methods: 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 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. Results: A 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. Conclusions: Response 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.

Original languageEnglish
Pages (from-to)846-854
Number of pages9
JournalClinical Cancer Research
Issue number4
Publication statusPublished - 2020 Feb 15

Bibliographical note

Funding Information:
The authors thank the patients, their families and caregivers, and the site investigators and staff for their participation in this study, and Christopher Morehouse of AstraZeneca for performing biomarker analyses. This study was funded by AstraZeneca. Medical writing support was provided by Ailsa Bennett, PhD, of SciMentum, Inc. (Nucleus Global), London, UK, and was funded by AstraZeneca.

Publisher Copyright:
©2019 American Association for Cancer Research.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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