Song Yuqin, Ma Jun, Zhang Huilai, Xie Yan, Peng Zhigang, Shuang Yuerong, Li Fei, Li Yufu, Yang Haiyan, Zou Liqun, Sun Xiuhua, Zhao Weili, Huang Wenrong, Huang Yunhong, Zhou Hui, Wang Yifan, Wang Weiwei, Xu Jing, Deng Rong, Meng Qin, Zhu Jun
Peking University Cancer Hospital & Institute, Beijing, China.
Harbin Institute of Hematology & Oncology, Harbin, China.
Nat Commun. 2025 May 16;16(1):4559. doi: 10.1038/s41467-025-59461-3.
Preclinical studies of tifcemalimab (anti-BTLA antibody) in combination with toripalimab (anti-PD-1 antibody) demonstrated synergistic anti-tumor effects. We present the outcomes of tifcemalimab with or without toripalimab in lymphoma patients. This is a 2-part, phase I study (NCT04477772). In Part A (dose escalation based on 3 + 3 design), patients with relapsed or refractory lymphoma received tifcemalimab monotherapy 1, 3 or 10 mg/kg for dose escalation and 3 mg/kg or 200 mg for dose expansion. For Part B (indication expansion), only classical Hodgkin's lymphoma (cHL) patients were included to receive tifcemalimab 100 or 200 mg plus toripalimab 240 mg due to poor tumor response in other subtypes. The primary endpoints were safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). 25 patients in Part A and 46 in Part B were enrolled. No dose-limiting toxicities were observed, and MTD was not reached. The RP2D for tifcemalimab was 200 mg. Adverse events were predominantly Grade 1/2. Grade 3/4 treatment-related adverse events occurred in 3 patients (12·0%) in Part A and 15 patients (32·6%) in Part B. No fatal adverse events were observed. Tifcemalimab with or without toripalimab demonstrated a favorable safety profile in lymphoma patients.
替西马洛单抗（抗BTLA抗体）与托瑞帕利单抗（抗PD-1抗体）联合使用的临床前研究显示出协同抗肿瘤作用。我们展示了替西马洛单抗联合或不联合托瑞帕利单抗治疗淋巴瘤患者的结果。这是一项分为两部分的I期研究（NCT04477772）。在A部分（基于3+3设计的剂量递增），复发或难治性淋巴瘤患者接受替西马洛单抗单药治疗，剂量递增阶段为1、3或10mg/kg，剂量扩展阶段为3mg/kg或200mg。对于B部分（适应症扩展），由于其他亚型的肿瘤反应较差，仅纳入经典霍奇金淋巴瘤（cHL）患者接受100或200mg替西马洛单抗加240mg托瑞帕利单抗治疗。主要终点为安全性、最大耐受剂量（MTD）和推荐的2期剂量（RP2D）。A部分纳入25例患者，B部分纳入46例患者。未观察到剂量限制性毒性，未达到MTD。替西马洛单抗的RP2D为200mg。不良事件主要为1/2级。3例（12.0%）A部分患者和15例（32.6%）B部分患者发生3/4级治疗相关不良事件。未观察到致命不良事件。替西马洛单抗联合或不联合托瑞帕利单抗在淋巴瘤患者中显示出良好的安全性。
