A phase I study of the OX40 agonist BGB-A445 with or without tislelizumab, an anti–PD-1 monoclonal antibody, in patients with advanced solid tumors: dose-escalation results

作者：Jayesh Desai, Sanjeev Deva, Bo Gao, Kunyu Yang, Kenneth J. O’Byrne, Meili Sun, Tianshu Liu, Tarek Meniawy, Xinmin Yu, Mark Voskoboynik, Diwakar Davar, Marco Matos, Shiangjiin Leaw, Tahmina Rahman, Xiaofei Qu, Hugh Giovinazzo, Xin Chen, Yan Dong, Daphne Day · 发表于：Cancer Chemotherapy and Pharmacology · 年份：2025 · DOI：10.1007/s00280-025-04809-1 · 被引用次数：4 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、CAR-T cell therapy research

PURPOSE: OX40 may stimulate T-cell activation, potentially enhanced with checkpointinhibition. Results are from the dose-escalation part of an ongoing, multicenter, open-label study (NCT04215978, registered 30 December 2019) investigating OX40 agonist BGB-A445 alone or with anti-PD-1 antibody tislelizumab in patients with advanced solid tumors. METHODS: Adults ≥18 years with previously treated advanced solid tumors, measurable by RECIST v1.1, enrolled. Dose-escalation A: 8 cohorts received increasing doses of IV BGB-A445 as monotherapy (20, 60, 150, 300, 600, 1200, 2400, 3600 mg); dose-escalation B: 6 cohorts received increasing doses of IV BGB-A445 (150, 300, 600, 1200, 2400, 3600 mg) + IV tislelizumab 200 mg. Primary objectives were safety and tolerability; secondary objectives included overall response rate (ORR) and pharmacokinetics. RESULTS: 112 patients were treated (A, n=63; B, n=49); 34/112 (30.4%) previously received checkpoint inhibitors. Treatment-related adverse events occurred in 36 (57.1%) (A) and 37 (75.5%) (B) patients, were grade ≥3 in 4 (6.3%) and 9 (18.4%), and caused treatment discontinuations in 1 (1.6%) and 1 (2.0%), respectively. Immune-mediated adverse events occurred in 8 (12.7%) (A) and 18 (36.7%) (B) patients, and infusion-related reactions in 9 (14.3%) (A) and 9 (18.4%) (B). No dose-limiting toxicities occurred. Unconfirmed ORR was 3.3% (unconfirmed partial response [PR], n=2) (A); confirmed was 21.3% (including PR, n=10) (B). BGB-A445 exposure inc...