First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors

作者：Yuanyuan Zhao, Yuxiang Ma, Aimin Zang, Ying Cheng, Yiping Zhang, Xiangcai Wang, Zhendong Chen, Song Qu, Jianbo He, Chuanben Chen, Chuan Jin, Dongyuan Zhu, Qingshan Li, Xianling Liu, Wuyun Su, Yi Ba, Yanrong Hao, Junmin Chen, Guoping Zhang, Shenhong Qu, Yong Li, Weineng Feng, Mengxiang Yang, Baorui Liu, Weiwei Ouyang, Liang Jin, Zhuang Yu, Xiaoyan Kang, Shilin Xue, Guihong Yang, Wei Yan, Yingying Yang, Zhi Liu, Yufeng Peng, Bill Fanslow, Xian Huang, Li Zhang, Hongyun Zhao · 发表于：Journal of Hematology & Oncology · 年份：2023 · DOI：10.1186/s13045-023-01445-1 · 被引用次数：57 · 研究领域：Cancer Immunotherapy and Biomarkers、Diabetes and associated disorders、Peptidase Inhibition and Analysis

BACKGROUND: ) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. METHODS: In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. RESULTS: Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR)...