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.

Abstract

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, including incidences of adverse events (AEs) and serious AEs. Secondary endpoints include objective response rate (ORR), disease control rate, duration of response, immunogenicity, and PK. The Phase 1b primary endpoint is progression-free survival (extensive-stage small cell lung cancer cohort) or ORR (GI and other solid tumors cohort). Secondary endpoints include additional efficacy assessments, PK, safety and tolerability. For Phase 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 conducted 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. This abstract was previously submitted to the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2024 and is submitted on behalf of the original authors with their permission. Funding: GSK (Study 223054). Medical writing support was provided by Avalere Health, funded by GSK. Clinical trial information: NCT05830123 .