TY - JOUR
T1 - Safety and efficacy of durvalumab and tremelimumab alone or in combination in patients with advanced gastric and gastroesophageal junction adenocarcinoma
AU - Kelly, Ronan J.
AU - Lee, Jeeyun
AU - Bang, Yung Jue
AU - Almhanna, Khaldoun
AU - Blum-Murphy, Mariela
AU - Catenacci, Daniel V.T.
AU - Chung, Hyun Cheol
AU - Wainberg, Zev A.
AU - Gibson, Michael K.
AU - Lee, Keun Wook
AU - Bendell, Johanna C.
AU - Denlinger, Crystal S.
AU - Chee, Cheng Ean
AU - Omori, Takeshi
AU - Leidner, Rom
AU - Lenz, Heinz Josef
AU - Chao, Yee
AU - Rebelatto, Marlon C.
AU - Brohawn, Philip Z.
AU - He, Peng
AU - McDevitt, Jennifer
AU - Sheth, Siddharth
AU - Englert, Judson M.
AU - Ku, Geoffrey Y.
N1 - Publisher Copyright:
©2019 American Association for Cancer Research.
PY - 2020/2/15
Y1 - 2020/2/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-19-2443
DO - 10.1158/1078-0432.CCR-19-2443
M3 - Article
C2 - 31676670
AN - SCOPUS:85079410465
SN - 1078-0432
VL - 26
SP - 846
EP - 854
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -