Phase 1/2 mocertatug rezetecan B7-H4–targeted topoisomerase I ADC combinations in gynecologic tumors.

GlaxoSmithKline’s BEHOLD-2 is a Phase 1/2 randomized, multi-cohort combination study testing mocertatug rezetecan (Mo‑Rez; a B7‑H4–directed antibody-drug conjugate delivering an exatecan-derived topoisomerase I inhibitor payload) with established agents in advanced solid tumors, focused here on endometrial and ovarian/fallopian tube/primary peritoneal cancers. Module 1 evaluates Mo‑Rez plus dostarlimab (GSK’s anti–PD‑1 monoclonal antibody) in advanced/metastatic/recurrent endometrial cancer, including a mismatch-repair–proficient/microsatellite-stable (MMRp/MSS) population where checkpoint inhibitor benefit is typically limited. Module 2 evaluates Mo‑Rez with or without bevacizumab (Genentech/Roche’s anti‑VEGF monoclonal antibody) in advanced ovarian/fallopian/peritoneal cancer, including platinum-pretreated and relapsed/refractory cohorts. The commercial/scientific angle is pushing a B7‑H4 ADC platform (B7‑H4 is highly prevalent in these tumors) into rational combinations to deepen responses and extend durability beyond what single-agent ADCs or IO can deliver. Today’s care for recurrent ovarian cancer is sequential systemic therapy (platinum re-challenge when appropriate, PARP inhibitors mainly in selected biomarker/maintenance settings, bevacizumab combinations, and later-line chemotherapy ± targeted agents); for advanced endometrial cancer it is carboplatin/paclitaxel upfront, with pembrolizumab + lenvatinib commonly used after progression for MMRp/MSS disease, and this trial explores an ADC-based backbone to improve outcomes where resistance is common.