A phase Ib/II, multicenter, open-label study of AK104, a PD-1/CTLA-4 bispecific antibody, combined with chemotherapy (chemo) as first-line therapy for advanced gastric (G) or gastroesophageal junction (GEJ) cancer: 2-Year update data.

作者：Jiafu Ji, Lin Shen, Ziyu Li, Xiangyu Gao, Ke Ji, Ye Chen, Nong Xu, Tianshu Liu, Nong Yang, Haijun Zhong, Changzheng Li, Zengqing Guo, Qingxia Fan, Xiaoyan Lin, Zhifang Yao, Wei Liu, Zhongmin Maxwell Wang, Baiyong Li, Yu Xia · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.4031 · 被引用次数：17 · 研究领域：Peptidase Inhibition and Analysis、Cancer Immunotherapy and Biomarkers、Monoclonal and Polyclonal Antibodies Research

4031 Background: Anti-PD-1 monoclonal antibodies plus chemo as first-line therapy for advanced G/GEJ cancer yields OS and PFS benefits compared to chemo alone while the survival benefits are limited, especially in patients with low PD-L1 expression (CPS<5). Simultaneous blockade of the PD-1 and CTLA-4 pathways has shown synergistic anti-tumor activity and has been proven effective across multiple cancer types. This phase Ib/Ⅱ dose-escalation study evaluated the safety and efficacy of AK104, a PD-1/CTLA-4 bispecific antibody, combined with XELOX or modified XELOX (mXELOX) in the first-line treatment of G/GEJ cancer cohorts (NCT03852251). Methods: Pts with unresectable advanced G/GEJ adenocarcinoma and no prior systemic therapy, regardless of PD-L1 status, were enrolled, excluding known HER2-positive pts. Enrolled patients received AK104 (4 mg/kg, 6 mg/kg or 10 mg/kg Q2W, 10 mg/kg or 15mg/kg Q3W) + chemo (mXELOX Q2W or XELOX Q3W). The primary endpoint was safety and the objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Results: As of 31 Oct. 2022, 98 pts were enrolled with only 4 pts in 10 mg/kg Q3W, the safety and efficacy of the regimen of 10mg/kg Q3W will be reported in the phase III study and not be reported here. 94 pts were enrolled with median age of 62.7 years (range: 29–75), 70.2% male, 62.8% ECOG PS 1, and 45.7% liver metastasis. The median follow-up was 24.0 months (range: 0.5-33.3). 88 patients (94%) ha...