A B7H3-targeting antibody–drug conjugate in advanced solid tumors: a phase 1/1b trial

作者：Yuxiang Ma, Yunpeng Yang, Yan Huang, Wen‐Feng Fang, Jinhui Xue, Xiangjiao Meng, Yun Fan, Siqing Fu, Lin Wu, Yulong Zheng, Jianjun Liu, Zhihua Liu, Zhuang Wu, Seth Rosen, S Q Qu, Bihui Li, Mingjun Li, Yanqiu Zhao, Shujun Yang, Yinghua Ji, David Sommerhalder, Suxia Luo, Kunyu Yang, Jingao Li, Dongqing Lv, Peng Zhang, Yuanyuan Zhao, Shaodong Hong, Yang Zhang, Shen Zhao, Steve Chin, Xianzhong Zhang, Wei Lian, Jiaqiang Cai, Tongtong Xue, Li Zhang, Hongyun Zhao · 发表于：Nature Medicine · 年份：2025 · DOI：10.1038/s41591-025-03600-2 · 被引用次数：88 · 研究领域：Radiopharmaceutical Chemistry and Applications、Boron Compounds in Chemistry、Peptidase Inhibition and Analysis

Antibody–drug conjugates (ADCs) have emerged as a transformative modality in the treatment of solid tumors. YL201, a novel B7H3-targeting ADC, leverages a tumor microenvironment activable linker-payload platform, coupled with a novel topoisomerase 1 inhibitor via a protease-cleavable linker. Here we report the findings from a large-scale, global, multicenter, phase 1 trial evaluating the safety, pharmacokinetics and preliminary efficacy of YL201 in patients with advanced solid tumors refractory to standard therapies. The trial included a dose-escalation part (phase 1) and a dose-expansion part (phase 1b). A total of 312 patients were enrolled across multiple tumor types, including extensive-stage small cell lung cancer (ES-SCLC), nasopharyngeal carcinoma (NPC), non-small cell lung cancer, esophageal squamous cell carcinoma and other solid tumors. The maximum tolerated dose was determined to be 2.8 mg kg−1, and the recommended expansion dose was selected as 2.0 mg kg−1 and 2.4 mg kg−1 every 3 weeks. The most common grade 3 or higher treatment-related adverse events included neutropenia (31.7%), leukopenia (29.5%) and anemia (25.0%). Only 4 cases of interstitial lung disease (1.3%) and 1 case of infusion reactions (0.3%) were observed. Encouraging anti-tumor activity was observed, particularly in patients with ES-SCLC (objective response rate (ORR), 63.9%), NPC (ORR, 48.6%), lung adenocarcinoma (ORR, 28.6%) and lymphoepithelioma-like carcinoma (ORR, 54.2%). No significant corre...