Efficacy and safety of LM-108, an anti-CCR8 monoclonal antibody, in combination with an anti-PD-1 antibody in patients with gastric cancer: Results from phase 1/2 studies.

作者：Jifang Gong, Chang Liu, Jun Yao, Junli Xue, Jing Dai, Yinghua Ji, Ben Markman, Alison Hiong, Xiuli Yang, Rusen Zhao, Yi Zheng, Qingshan Li, Jun Wu, Minal Barve, Mihitha Ariyapperuma, Gary Richardson, Xia Qin, Crystal Qin, Lin Shen · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.2504 · 被引用次数：12 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Peptidase Inhibition and Analysis、Chemokine receptors and signaling

2504 Background: Targeting tumor-infiltrating regulatory T cells (Tregs) is a potential approach to overcome immunotherapy resistance in the treatment of cancers. LM-108 is a novel Fc-optimized, anti-CCR8 monoclonal antibody that selectively depletes tumor-infiltrating Tregs. Here we report a pooled analysis of results from 3 phase 1/2 studies (NCT05199753; NCT05255484; NCT05518045) to evaluate the efficacy and safety of LM-108 in combination with anti-PD-1 therapy in patients with gastric cancer. Methods: Eligible patients with gastric cancer treated with LM-108 in combination with an anti-PD-1 antibody were included in the analysis. Patients received intravenous LM-108 at dose levels of 3 mg/kg Q2W, 6 mg/kg Q3W, or 10 mg/kg Q3W plus an anti-PD-1 antibody (intravenous pembrolizumab 200 mg Q3W or 400 mg Q6W or toripalimab 240 mg Q3W). The primary endpoint was investigator-assessed ORR per RECIST v1.1. The secondary endpoints included safety, other efficacy outcomes, and biomarkers analysis. Data cutoff date for the pooled analysis was December 25, 2023. Results: Forty-eight patients with gastric cancer (median age: 60.5 years; male: 72.9%) from China, USA, and Australia were treated ≥ 1 dose of LM-108 in combination with pembrolizumab or toripalimab. Most (n = 47, 97.9%) patients had received at least 1 prior anticancer treatment, and 43 (89.6%) had received prior anti-PD-1 therapy. Treatment-related adverse events (TRAEs) occurred in 39 (81.3%) patients, in which the most co...