A phase I clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of HLX43 (anti-PD-L1 ADC) in patients with advanced/metastatic solid tumors.

作者：Jie Wang, Rui Wan, Shan Zeng, Lin Wu, Hua Zhong, Jingxun Wu, Guowu Wu, Jianchun Duan, Shuqing Wei, Zhiye Zhang, Linlin Wang, Juan Li, Jingfeng Liu, Yu Chen, Xinjing Wang, Xiaoli Hou, Qingyu Wang, Haoyu Yu, Jing Li · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.3025 · 被引用次数：2 · 研究领域：Synthesis and Biological Evaluation、Multiple Myeloma Research and Treatments、Peptidase Inhibition and Analysis

3025 Background: Antigens highly expressed in tumors such as HER2 and TROP2 have been widely investigated as antibody-drug conjugate (ADC) targets, leading to their approval for various cancers due to their promising efficacies. However, limited targets for approved ADCs and resistance to the cytotoxic agents render the imperative need for new ADCs. This study aimed to evaluate the safety, tolerability, and preliminary efficacy of HLX43, a novel anti-PD-L1 ADC in patients with advanced/metastatic solid tumors. Methods: This phase 1 study consisted of 2 parts. Parts 1 and 2 were dose escalation and dose expansion phases, respectively, to explore different doses of HLX43. In Part 1, patients with histologically or cytologically confirmed advanced/metastatic malignant solid tumors refractory to or not amenable to standard therapies received intravenous HLX43 at 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, or 4 mg/kg, Q3W. In Part 2, patients with advanced/metastatic non-small cell lung cancer (NSCLC) refractory to standard treatment received HLX43 at 2 mg/kg, 2.5 mg/kg, or 3 mg/kg, Q3W. The primary endpoints for Part 1 were the proportion of subjects experiencing dose-limiting toxicity (DLT) in each dose group within three weeks after the first drug administration and the maximum tolerable dose (MTD) while that for Part 2 were the recommended Phase 2 dose and IRRC-assessed objective response rate (ORR). Results: As of 27 June 2023, 18 patients with non-small cell lung cancer (n = 12, 6...