Abstract CT188: BEHOLD-1: A Phase 1 Dose Escalation Study of GSK5733584, a B7-H4-Targeted Antibody-Drug Conjugate, in Patients With Advanced Solid Tumors, Including Dose Expansion in Patients With Endometrial and Platinum-Resistant Ovarian Cancer

Abstract Background: B7-homolog 4 (B7-H4), a transmembrane glycoprotein with a multifaceted immunoregulatory role in cancer, is overexpressed in solid tumors, including ovarian (OC) and endometrial cancer (EC), with limited expression in normal tissue. GSK5733584 (GSK’584; HS-20089) is an antibody-drug conjugate comprising a humanized anti-B7-H4 immunoglobulin G1 monoclonal antibody linked to rezetecan, a topoisomerase 1 inhibitor (HS-9265), via a stable protease-cleavable tetrapeptide (GGFG) linker (average drug:antibody ratio of 6). GSK’584 showed preliminary antitumor activity and acceptable safety in a Phase 1 study in Chinese patients with recurrent/metastatic solid tumors (unselected for B7-H4 expression). The current study (NCT06431594) will evaluate GSK’584 in patients with advanced solid tumors, including platinum-resistant OC (PROC) and EC. Methods: This two-part, multiregional, open-label Phase 1 study is enrolling adult patients with ECOG PS 0-2, measurable disease per RECIST 1.1, and no prior anti-B7-H4 therapy. Part 1a (dose escalation) assesses safety, tolerability, pharmacokinetics (PK), and immunogenicity of GSK’584 in 26-40 patients with advanced solid tumors refractory/intolerant to established therapies. Dose escalation will use a rolling six design with planned doses of 2.8, 4.8, 5.8, and 7.2 mg/kg (Q3W until progression, toxicity, or death). Part 1b (dose expansion) assesses clinical activity, safety, and PK of GSK’584 in PROC (N≈90) and EC (N≈60) expansion cohorts in 2-3 selected dose levels. In Part 1a, the primary endpoint is dose-limiting toxicity incidence. Secondary endpoints include confirmed objective response rate (ORR), duration of response (DoR), progression-free survival (PFS; all per RECIST 1.1, investigator assessment), safety, PK, and immunogenicity. In part 1b, the primary endpoint is confirmed ORR per RECIST 1.1 by investigator assessment. Secondary endpoints include DoR, PFS (per RECIST 1.1, investigator assessment), OS, cancer antigen 125 (CA-125) response rate (PROC only), safety, PK, and immunogenicity. Exploratory endpoints include retrospective correlation of B7-H4 expression and GSK’584 exposure/response, additional correlative biomarker/PK investigations, and patient-reported outcomes (part 1b only). Safety will be assessed throughout until 90 days post-last dose. Efficacy will be assessed by imaging at baseline, Q6W for 24 weeks, then Q12W until progression or exit from study. CA-125 (PROC only) will be assessed Q3W until progression or exit from study. Tissue, blood, and urine samples will be collected for biomarker/PK evaluations. Results will be reported using descriptive statistics and 95% confidence intervals. This abstract was previously presented at SGO 2025. Funding: GSK (study 222730). Citation Format: William McKean, Philippe L. Bedard, Phuong Dinh, Dhabusha Sabanathan, Toon Van Gorp, John Hilton, Katriina Jalkanen, Isabelle Ray-Coquard, Domenica Lorusso, Shigehisa Kitano, Marloes GJ Van Rijn-Van Drongen, Valentina Boni, Victor Moreno, Lisa Liu Burström, Alexander Philipovskiy, Alina Goetz, Julie Holden, Shruti Shah, Jeremy Waight, Francisco J. Gonzalez Carreras, Antonio Riccio, Morrys C. Kaisermann, Jennifer Veneris, Minal Barve. BEHOLD-1: A Phase 1 Dose Escalation Study of GSK5733584, a B7-H4-Targeted Antibody-Drug Conjugate, in Patients With Advanced Solid Tumors, Including Dose Expansion in Patients With Endometrial and Platinum-Resistant Ovarian Cancer [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 CT188.