A phase 1 dose escalation/expansion study of GSK5764227 (GSK’227), a B7-homolog 3 (B7-H3) protein targeted antibody-drug conjugate (ADC), in patients with advanced solid tumors, including gastrointestinal (GI) cancers.

作者：Wasif M. Saif, Philippe A. Cassier, Giuseppe Curigliano, Gennaro Daniele, John Hilton, Shigehiro Koganemaru, Rubén Dario Kowalyszyn, Patricia LoRusso, Vı́ctor Moreno, M.E. Olmedo García, Herman Andrés Perroud, Stefan N. Symeonides, Noboru Yamamoto, Amine Aziez, Rana Anjum, John LaMacchia, Harjeet Sembhi, Nirav Ratia, Antoine Italiano · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.4_suppl.tps847 · 被引用次数：4 · 研究领域：HER2/EGFR in Cancer Research、Colorectal Cancer Treatments and Studies、Radiomics and Machine Learning in Medical Imaging

TPS847 Background: B7-H3 is an immune checkpoint protein overexpressed in multiple solid tumors with limited expression in normal tissues. GSK’227 (HS-20093), a novel B7-H3-targeted ADC, is composed of a human anti–B7-H3 monoclonal antibody linked to a topoisomerase I inhibitor via a protease-cleavable linker, and has shown acceptable safety and promising antitumor activity in patients of Asian origin with advanced solid tumors (NCT05276609; NCT05830123). The current study will evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of GSK’227 in patients with solid tumors, including GI cancers, in a global population. Methods: This two-part (dose-escalation [1a] and expansion [1b]) global, open-label, Phase I study (NCT06551142) will enroll ~260 patients, with enrollment currently ongoing. Key eligibility includes: aged ≥18 years, histologically confirmed advanced solid tumors, including those with colorectal cancer, esophageal squamous cell carcinoma, and pancreatic cancer, with measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no prior B7-H3 treatment. Eligible patients will receive intravenous GSK’227 every 3 weeks (Q3W) until progression, toxicity, loss to follow-up, or death. For Phase 1a, a Bayesian optimal interval design will be used to determine the maximum tolerated dose. Phase 1a primary endpoints are safety and tolerability, includi...