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

Desai, J; Deva, S; Gao, B; Yang, K; O&#39;Byrne, KJ; Sun, M; Liu, T; Meniawy, T; Yu, X; Voskoboynik, M; Davar, D; Matos, M; Leaw, S; Rahman, T; Qu, X; Giovinazzo, H; Chen, X; Dong, Y; Day, D

Author(s): Desai, J; Deva, S; Gao, B; Yang, K; O'Byrne, KJ; Sun, M; Liu, T; Meniawy, T; Yu, X; Voskoboynik, M; Davar, D; Matos, M; Leaw, S; Rahman, T; Qu, X; Giovinazzo, H; Chen, X; Dong, Y; Day, D;
Details: Publication Year 2025-10-08,Volume 95,Issue #1,Page 99
Journal Title: Cancer Chemotherapy and Pharmacology
Publication Type: Research article
Abstract: 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 increased dose-proportionally with a half-life of 8-13 days. OX40 receptor occupancy was saturated at ≥300 mg BGB-A445 in all cohorts. CONCLUSION: BGB-A445 was well tolerated and demonstrated on-target immune activation at clinically relevant doses. Antitumor activity was observed across cohorts.
Publisher: Springer Nature
Keywords: Humans; *Antibodies, Monoclonal, Humanized/administration & dosage/adverse; effects/pharmacokinetics; Female; Male; Middle Aged; *Neoplasms/drug therapy/pathology; Aged; Adult; *Receptors, OX40/agonists; Dose-Response Relationship, Drug; *Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse; effects/pharmacokinetics/therapeutic use; Programmed Cell Death 1 Receptor/antagonists & inhibitors; Maximum Tolerated Dose; Advanced solid tumors; Immune checkpoint inhibitors; Ox40; Pd-1; Phase I clinical trial; Tislelizumab
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1007/s00280-025-04809-1
Open Access at Publisher's Site: https://doi.org/10.1007/s00280-025-04809-1
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-11-06 02:44:49

Last Modified: 2025-11-06 02:44:58