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

Research output: Contribution to journalArticle

Abstract

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
Volume26
Issue number4
DOIs
Publication statusPublished - 2020 Feb 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Kelly, R. J., Lee, J., Bang, Y. J., Almhanna, K., Blum-Murphy, M., Catenacci, D. V. T., Chung, H. C., Wainberg, Z. A., Gibson, M. K., Lee, K. W., Bendell, J. C., Denlinger, C. S., Chee, C. E., Omori, T., Leidner, R., Lenz, H. J., Chao, Y., Rebelatto, M. C., Brohawn, P. Z., ... Ku, G. Y. (2020). Safety and efficacy of durvalumab and tremelimumab alone or in combination in patients with advanced gastric and gastroesophageal junction adenocarcinoma. Clinical Cancer Research, 26(4), 846-854. https://doi.org/10.1158/1078-0432.CCR-19-2443