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

Authors

null

Yanchun Meng

Phase I Clinical Trial Center, Fudan University Shanghai Cancer Center, Shanghai, China

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

Organizations

Phase I Clinical Trial Center, Fudan University Shanghai Cancer Center, Shanghai, China, Chinese PLA General Hospital & Medical School, Beijing, China, Jilin Cancer Hospital, Changchun, China, Cancer Hospital of the University of Chinese Academy of Sciences Zhejiang Cancer Hospital, Hangzhou, China, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China, Linyi Cancer Hospital, Linyi, China, ImmuneOnco Biopharmaceuticals (Shanghai) Inc., Shanghai, China

Research Funding

Pharmaceutical/Biotech Company
ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

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 adverse events (TRAEs) occurred in all 16 subjects (100%), with 4 subjects (25%) reported to have grade 3 TRAEs. No subject discontinued IMM2902 treatment due to TRAEs. The most common TRAEs were platelet count decreased (62.5%), infusion related reaction (50%), and anemia (43.8%). The most common grade 3 or above TRAE was platelet count decreased (18.8%). One SAE (grade 3 gastrointestinal hemorrhage) was reported, which was unrelated to IMM2902. Among 13 evaluable subjects, 4 patients achieved SD (2 pts with gastric cancer at 0.1 mg/kg, 1 pt with skin cancer at 0.9 mg/kg, and 1 pt with breast cancer at 2.0 mg/kg). Preliminary PK analysis showed IMM2902 had a non-linear PK. Serum concentration of IMM2902 reached steady state after the third administration. Preliminary PD data showed that, beginning at 0.3 mg/kg, the number of peripheral CD3+ and CD8+ T-cells increased after 4 weeks of treatment. Conclusions: IMM2902 showed an encouraging preliminary safety, tolerability and anti-tumor activity up to 2.0 mg/kg. The phase I/II study is ongoing. Clinical trial information: ChiCTR20212375.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Other Developmental Therapeutics

Clinical Trial Registration Number

CTR20212375

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr e15185)

DOI

10.1200/JCO.2023.41.16_suppl.e15185

Abstract #

e15185

Abstract Disclosures