Tebotelimab, a PD-1/LAG-3 bispecific antibody, in patients with advanced hepatocellular carcinoma who had failed prior targeted therapy and/or immunotherapy: An open-label, single-arm, phase 1/2 dose-escalation and expansion study.

作者：Zhenggang Ren, Yabing Guo, Yuxian Bai, Jieer Ying, Zhiqiang Meng, Zhendong Chen, Shanzhi Gu, Jingdong Zhang, Jun Liang, Xinfang Hou, Wěi Li, Aibing Xu, Chunyi Hao, Jian Zhang, Ruijun Xing, Xinyu Zhang, Dan Zhang, Stephen L. Chan · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.4_suppl.578 · 被引用次数：24 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Pancreatic and Hepatic Oncology Research

578 Background: Immune checkpoint inhibitors (CPIs) targeting PD-1/PD-L1 have become established treatments for advanced hepatocellular carcinoma (aHCC) but yield low objective response rates (ORRs) in treated patients (pts). Dual inhibition of LAG-3 and PD-1 pathways has demonstrated synergy in activating T-cells and improving immune response. Tebotelimab, also known as MGD013, is a bispecific tetravalent DART molecule that can bind both PD-1 and LAG-3. We initiated an open-label, single-arm, phase 1/2 dose escalation and expansion study to assess the safety and efficacy of tebotelimab in pts with aHCC. Methods: Eligible pts with aHCC who received ≥1 prior systemic treatment with or without prior CPI exposure were enrolled. The dose escalation phase evaluated doses at 120, 240, 400, and 600 mg. Tebotelimab was administered intravenously once every two weeks (Q2W) on days 1 and 15 of each 28-day cycle. The dose expansion phase consisted of one CPI-experienced cohort and one CPI-naïve cohort, both treated at recommended phase 2 dose (RP2D). Primary endpoints were safety for the escalation phase, and safety and ORR per RECIST v1.1 for the expansion phase. Investigator-assessed efficacy results are reported. Results: At data cut-off as of 27 April 2022, 13 pts received tebotelimab in the escalation phase. No dose-limiting toxicity was observed and RP2D was determined as 600 mg Q2W. In the expansion phase, 69 pts (CPI-experienced 33, CPI-naïve 36) were enrolled (median age, 57.0 ...