1. Safety and Efficacy of Durvalumab and Tremelimumab Alone or in Combination in Patients with Advanced Gastric and Gastroesophageal Junction Adenocarcinoma
- Author
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Kelly, Ronan J, Lee, Jeeyun, Bang, Yung-Jue, Almhanna, Khaldoun, Blum-Murphy, Mariela, Catenacci, Daniel VT, 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 Z, He, Peng, McDevitt, Jennifer, Sheth, Siddharth, Englert, Judson M, and Ku, Geoffrey Y
- Subjects
Clinical Research ,Cancer ,Rare Diseases ,Clinical Trials and Supportive Activities ,Digestive Diseases ,Patient Safety ,6.2 Cellular and gene therapies ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adenocarcinoma ,Adult ,Aged ,Aged ,80 and over ,Antibodies ,Monoclonal ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Combined Chemotherapy Protocols ,B7-H1 Antigen ,CTLA-4 Antigen ,Circulating Tumor DNA ,Esophagogastric Junction ,Female ,Humans ,Interferon-gamma ,Male ,Middle Aged ,Prospective Studies ,Stomach Neoplasms ,Transcriptome ,Young Adult ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
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.
- Published
- 2020