Mocertatug rezetecan (GSK5733584), a B7-H4-targeted antibody-drug conjugate (ADC), in platinum-resistant ovarian cancer (PROC) and endometrial cancer (EC): First results from the global BEHOLD-1 study

Abstract

Objectives: Mocertatug rezetecan (Mo-Rez, GSK5733584) is a novel ADC comprised of a humanised IgG1 monoclonal anti-B7-H4 antibody conjugated to rezetecan (topoisomerase 1 inhibitor-payload complex) via a protease cleavable linker (Drug-Antibody ratio: 6) that has shown promising antitumour activity in Chinese patients (pts) with PROC.1 We report first data from the global BEHOLD-1 (NCT06431594) trial of Mo-Rez monotherapy in pts. with PROC or recurrent EC unselected for B7-H4 tumor expression. Method(s): BEHOLD-1 is a 2-part, open-label, Phase 1 study. Phase 1a dose escalation (rolling 6 design to determine maximum tolerated dose [MTD]) planned to assess up to 4 Mo-Rez dose levels given intravenously every 3 weeks (Q3W) until progression/toxicity in pts. with advanced solid tumors. In Phase 1b dose expansion, pts. with PROC or EC (1-3 prior lines of therapy) were randomized to 3 or 2 Mo-Rez dose levels, respectively. Primary endpoints: incidence of dose- limiting toxicity (DLT-evaluable; Phase 1a); confirmed overall response rate (ORR) by investigator per RECIST 1.1 (Phase 1b). Funding(s): GSK (222730). Writing support provided by Avalere Health, funded by GSK. Result(s): A total of 224 pts. were enrolled (Phase 1a: n = 44 [21 OC], data cut-off [DCO] 1 Jul 2025; Phase 1b: n = 180 [n = 131 PROC, n = 49 EC]; DCO 12 Nov 2025). In Phase 1a, of 16 DLT-evaluable pts., 1 experienced 2 DLTs (febrile neutropenia and thrombocytopenia) at 5.8 mg/kg Q3W. MTD was not reached; maximum applicable dose was 5.8 mg/kg Q3W. In Phase 1b, 130 pts. with PROC and 48 pts. with EC received >=1 dose at DCO. Median follow-up was 6.1 and 4.0 months in PROC and EC, respectively. At highest dose levels, 5.8 mg/kg Q3W for PROC and 4.8 mg/kg Q3W for EC, confirmed ORR was 62% and 67%, respectively (Table). Median duration of response was not reached. In Phase 1b, the most common treatment-related adverse event (TRAE) was nausea (68%, PROC; 67% EC). Gr >= 3 TRAEs occurred in 42% and 35% pts. with PROC and EC, respectively, and were mostly hematologic (most common: neutrophil count decrease [15% in both PROC and EC]; neutropenia [12% and 6%]; and anemia [8% and 15%]); frequency of these events was dose-dependent as were dose delay/reductions, indicating a dose-dependent impact on tolerability. Treatment discontinuation due to TRAEs was low (2% in PROC, 4% in EC). Conclusion(s): Mo-Rez showed encouraging antitumour activity in pts. with PROC and EC and had a manageable safety profile. Mo-Rez is being evaluated in global Phase 3 trials in PROC (NCT07286266) and recurrent EC (NCT07286331). Reference: Yuan G, et al. Ann Oncol. 2025;36(Suppl 2):S717-18. [Formula presented] Copyright © 2026