| Popis: |
Background: The ecto-ATPase CD39 is the rate-limiting enzyme in the adenosine pathway that plays an important immune regulatory role. Preclinically, inhibition of CD39 by TTX-030, a first-in-class fully human anti-CD39 antibody, reversed immunosuppression by maintaining high levels of immune-stimulatory extracellular ATP while reducing suppressive adenosine. The addition of nivolumab to chemotherapy has recently become the standard of care of 1st-line (1L) treatment of locally advanced or metastatic (LA/M) gastric cancer but further improvements are needed. Methods: An expansion cohort of Study TTX-030-002 (ongoing, US and South Korea) is evaluating the safety and efficacy of the combination of TTX-030, budigalimab (anti-PD-1) and FOLFOX for the 1L treatment of patients (pts) with LA/M HER2− gastric/GEJ adenocarcinoma. The primary objective was to assess safety and tolerability. Secondary endpoints included ORR by RECIST/iRECIST, and PFS. Correlative studies included the analysis of intratumoral expression of CD39 and PD-L1. Results: Forty-four pts were enrolled with the median age [range] of 61 [30−81] years, 41% were female, and 57% were Asian. Pts had an ECOG of 0 (39%) or 1 (61%), 70% had gastric adenocarcinoma, 30% had GEJ adenocarcinoma. As of the safety data cutoff (Nov 19, 2021), 39 pts (89%) experienced at least 1 treatment-emergent AE (any Grade, regardless of relatedness). Twenty-one pts (48%) experienced at least 1 AE considered related to TTX-030 (any Grade); five (11%) experienced a Grade 3/4 AE considered related to TTX-030. There were no Grade 5 TEAEs. Eleven pts (25%) had experienced SAEs; none were considered related to TTX-030. The most common AEs by preferred term (any Grade, regardless of relatedness) in ≥10 pts were nausea (52%), neutrophil count decreased (39%), decreased appetite (30%), diarrhea (25%), and fatigue (23%). The most common Grade ≥3 AEs (regardless of relatedness) in ≥2 pts were neutrophil count decreased (27%), febrile neutropenia (5%), hypokalemia (5%). As of the efficacy data cutoff (Dec 2, 2021), the median time [range] on study was 139 [8−375] days. Among 38 efficacy evaluable pts, 23 pts experienced PR or better as best response (PR: n=21; CR: n=2; ORR=61%), 12 experienced SD, and 3 had PD. Thirty-six of the 38 efficacy-evaluable patients had known PD-L1 Combined Positive Score (CPS); response rates were 4/10 (CPS Conclusions: Preliminary results indicate that the combination of TTX-030, budigalimab and FOLFOX exhibited promising efficacy as 1L treatment of LA/M gastric/GEJ cancer regardless of CPS status and has a manageable safety profile without evidence of excessive toxicities. To our knowledge, this represents the first report of an anti-CD39 antibody in combination with chemo-immunotherapy in gastric cancer. Updated clinical and biomarker data will be included in the final presentation. Citation Format: Zev Wainberg, Yoon-Koo Kang, Keun-Wook Lee, Seung Tae Kim, Joseph Chao, Daniel Catenacci, Sung Yong Oh, Heloisa P. Soares, J. Eva Selfridge, Yongjun Cha, Roland T. Skeel, Hyung-Don Kim, Anh Tran, Achim Moesta, Tracy Dela Cruz, Anil Singhal, Thomas M. Jahn, Farshid Dayyani. Safety and efficacy of TTX-030, an anti-CD39 antibody, in combination with chemoimmunotherapy for the first line treatment of locally advanced or metastatic gastric/GEJ cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT015. |
