Abstract CT195: A phase 1 dose escalation/expansion study of GSK5764227, a B7-homolog 3 protein targeted antibody-drug conjugate, in combination with standard of care in patients with advanced solid tumors

Abstract Background: B7-homolog 3 protein (B7-H3) is an immune checkpoint protein overexpressed in many types of solid tumors, but with limited expression in normal tissues [1]. GSK5764227 (GSK’227) is a novel antibody-drug conjugate (ADC) composed of a fully human anti-B7-H3 monoclonal antibody linked to a topoisomerase I inhibitor via a protease-cleavable linker. GSK’227 (also known as HS-20093) has shown acceptable safety and promising antitumor activity in Asian patients with advanced solid tumors (NCT05276609; NCT05830123). The current study (NCT06551142) will evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of GSK’227 as monotherapy (study design previously presented [2]), and in combination with standard of care (SoC), in patients with advanced solid tumors in a global population. Methods: This two-part (dose-escalation [1a] and expansion [1b]) global, open-label, Phase I study will enroll ∼280 adult patients with histologically confirmed advanced solid tumors and progression on/intolerance to SoC, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group performance status 0-1, and no prior anti-B7-H3 therapy. Phase 1a will investigate GSK’227 dose escalation as monotherapy [2], and in combination with SoC. Patients will receive intravenous GSK’227 every 3 weeks (Q3W) as monotherapy or in combination with SoC (Combination [Comb.] 1: cisplatin/carboplatin + atezolizumab/durvalumab/pembrolizumab; Comb. 2: atezolizumab/durvalumab/pembrolizumab; Comb. 3: folinic acid + fluorouracil [FOLF] + bevacizumab; Comb. 4: FOLF + cetuximab) until progression, toxicity, loss to follow-up, or death. Phase 1a primary endpoints are safety and tolerability, including incidences of adverse events (AEs) and serious AEs. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), immunogenicity, and PK. The Phase 1b dose expansion will include multiple solid tumor cohorts [2]. The primary endpoint for 1b is ORR, and secondary endpoints include progression-free survival, DCR, DoR, PK, safety, and tolerability. For 1a and 1b, efficacy will be assessed per RECIST v1.1, with imaging conducted Q6W from first dose then Q12W after 24 weeks. Safety follow-up will be assessed at 30, 60, and 90 (±7) days after the last dose. Safety, tolerability, and efficacy analyses will be conducted using descriptive statistics and, for efficacy analyses, point estimates with 2-sided 95% confidence intervals. Funding: GSK (Study 223054). Medical writing support provided by Avalere Health, funded by GSK. 1. Khan M, et al. Front Immunol. 2021;12:651634. 2. Curigliano G, et al. Presented at ESMO-IO 2024 (Poster 168TiP), 11-13 Dec, Geneva, Switzerland. Citation Format: Hye Ryun Kim, Philippe Cassier, Gennaro Daniele, Giuseppe Curigliano, John Hilton, Antoine Italiano, Shigehiro Koganemaru, Ruben Kowalyszyn, Patricia LoRusso, Victor Moreno, Maria Eugenia Olmedo Garcia, Herman Perroud, Wasif Saif, Noboru Yamamoto, Amine Aziez, Rana Anjum, John LaMacchia, Ravi Kasinathan, Stefan Symeonides, Jireh Huang, Vivek Subbiah. A phase 1 dose escalation/expansion study of GSK5764227, a B7-homolog 3 protein targeted antibody-drug conjugate, in combination with standard of care in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT195.