Preliminary results of a phase I, first-in-human, dose escalation study of IMM2902 in patients with HER2-expressing advanced solid tumors.

作者：Yanchun Meng, Jian Zhang, Chuanhua Zhao, Ying Cheng, Liming Zhu, Zhengbo Song, Nong Xu, Zhen Wang, Yanping Wang, Yiqun Du, Deqiang Jing, Dinglu Chen, Qiaofeng Qu, Xiwen Zhao, Wei Li, Qiying Lu, Wenzhi Tian, Jianming Xu · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.e15185 · 被引用次数：7 · 研究领域：Phagocytosis and Immune Regulation、Adenosine and Purinergic Signaling、Pancreatic function and diabetes

e15185 Background: IMM2902 is a novel recombinant bispecific fusion protein containing SIRPα binding domain trapped to the light chain of a humanized anti-HER2 antibody. With its high affinity to HER2 and CD47 on tumor cell membrane, IMM2902 can drive several anti-tumoral killing mechanisms such as directly targeting HER2 expressing tumor cells; restoring the phagocytic function of macrophages against tumor cells via CD47-SIRPα blockade; activating NK cells and macrophages mediated antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC); and most importantly, inducing accelerated HER2 internalization and degradation. Phase I dose escalation studies of IMM2902 in advanced solid tumors are conducted in both China and the United States, here we present the preliminary results from China trial. Methods: The dose escalation study of IMM2902 was conducted following a modified 3+3 design to evaluate the safety and tolerability of the study drug and to determine the MTD/RP2D. IMM2902 was administered intravenously every week (QW) in 4-week cycles, and the first cycle was the DLT observation period. The tumor responses were evaluated based on RECIST v1.1. IMM2902 pharmacokinetics (PK) and pharmacodynamics (PD) were also evaluated. Results: As of 26 December 2022, a total of 16 subjects had received at least one dose of IMM2902 in 5 dose cohorts (0.03, 0.1, 0.3, 0.9 and 2.0 mg/kg). Of the 16 subjects, no DLTs were observed. Treatment related ...