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

作者：Jifang Gong, Chang Liu, Liang Liu, Jun Yao, Yiping Mou, Jing Dai, Youshan Chen, Xiuli Yang, Mihitha Ariyapperuma, Yiping Zhang, Junli Xue, Jermaine Coward, Yun Zhou, Yinghua Ji, Qingshan Li, Rusen Zhao, Zhizhen Zhu, Ben Markman, Haoyuan Li, Lin Shen · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.4010 · 被引用次数：5 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Immunotherapy and Biomarkers、Chronic Lymphocytic Leukemia Research

4010 Background: Targeting tumor-infiltrating Tregs presents a promising strategy to overcome resistance to immunotherapy in cancer treatment. LM-108 is a novel Fc-optimized anti-CCR8 monoclonal antibody designed to selectively deplete tumor-infiltrating Tregs while sparing peripheral Tregs. This pooled analysis of two phase 1/2 trials assesses the efficacy and safety of LM-108 in combination with anti-PD-1 therapy in patients with pancreatic cancer. Methods: Eligible patients (pts) with pancreatic cancer who had progressed on or after at least one prior line of systemic therapy were included. Treatment regimens included LM-108 at doses of 3 mg/kg Q3W, 3 mg/kg Q2W, 10 mg/kg Q3W, or 10 mg/kg Q2W, in combination with pembrolizumab (400 mg Q6W) or toripalimab (240 mg Q3W). The primary endpoint was ORR. Secondary endpoints were DCR, PFS, OS, DoR, safety, and biomarkers analysis. Data cutoff: December 2, 2024. Results: A total of 80 pts (median age: 63 years; 58.8% male) from China and Australia were treated. Of these, 48 pts had progressed on or after 1 prior line of therapy, and 32 pts had ≥2 lines. Eighteen pts (22.5%) had prior anti-PD-1 therapy, and 52 pts (65.0%) had liver metastases at baseline. TRAEs were reported in 76 pts (95.0%). Common TRAEs (≥25%) included increased AST, increased ALT, anemia, rash, pyrexia, decreased platelet count and increased conjugated bilirubin. Grade ≥3 TRAEs occurred in 42 pts (52.5%), the most common events (≥5%) were lipase elevation (7.5%),...