Phase I Study of the Anti-Btla Antibody Tifcemalimab As a Single Agent or in Combination with Toripalimab in Relapsed/Refractory Lymphomas

作者：Jun Ma, Yuqin Song, Yan Xie, Huilai Zhang, Yue-Rong Shuang, Zhigang Peng, Fei Li, Yunhong Huang, Weili Zhao, Wenrong Huang, Yali Pan, Mingying Liu, Feiwu Ran, Hui Feng, Sheng Yao, Patricia Keegan, Jianjun Zou, Jun Zhu · 发表于：Blood · 年份：2022 · DOI：10.1182/blood-2022-157497 · 被引用次数：12 · 研究领域：Monoclonal and Polyclonal Antibodies Research、CAR-T cell therapy research、Lymphoma Diagnosis and Treatment

Background: The B- and T-lymphocyte attenuator (BTLA) is an inhibitory receptor expressed on B, T and NK cells. Using Peripheral Blood Mononuclear Cell (PBMC) derived from cancer patients, co-blockade of the BTLA and PD-1 pathways improved antigen specific T cell response compared to either blockade alone. Tifcemalimab (also known as icatolimab, JS004 or TAB004) is a humanized IgG4 monoclonal antibody with a hinge mutation (S228P) that binds BTLA and blocks its interaction with its ligand Herpesvirus Entry Mediator (HVEM). In this first-in-human study, we report the preliminary safety and anti-tumor activity of tifcemalimab as a single agent or in combination with toripalimab (anti-PD-1) in patients with relapsed/refractory (R/R) lymphoma. Methods: Eligible patients with R/R lymphoma were enrolled in this open-label, multicenter study (NCT04477772). Tifcemalimab was administered as a monotherapy at escalating doses of 1, 3 and 10 mg/kg intravenously Q3W, followed by 3 mg/kg and 200 mg monotherapy dose expansion until disease progression or intolerable toxicity. During combination dose escalation, patients received ascending doses of tifcemalimab (100mg and 200mg) plus toripalimab (240mg). Dose-limiting toxicity (DLT) was evaluated by a safety monitoring committee. Study objectives included safety, pharmacokinetics, and efficacy. Results: By the cutoff date of July 21, 2022, a total of 48 patients were enrolled, including 25 in the monotherapy and 23 in the combination subgrou...