Phase 3 PF-08634404 PD-1×VEGF bispecific antibody plus chemo vs pembrolizumab in pMMR endometrial cancer

Pfizer’s Symbiotic-GYN-18 (NCT07578649) is a Phase 3, open-label, randomized study testing whether PF-08634404—an investigational PD-1 and VEGF–targeted bispecific antibody—combined with standard chemotherapy improves outcomes versus pembrolizumab (Merck/MSD), a PD-1 (CD279) monoclonal antibody, combined with the same chemotherapy in first-line advanced or recurrent mismatch repair–proficient (pMMR) endometrial cancer. About 600 adults are randomized 1:1 to PF-08634404 + chemotherapy followed by PF-08634404 maintenance (up to ~2 years) or pembrolizumab + chemotherapy followed by pembrolizumab maintenance (up to ~2 years). Eligible participants have newly diagnosed measurable FIGO stage III, stage IV (with or without measurable disease), or recurrent disease where curative surgery/radiation is unlikely, and generally have not had prior systemic chemotherapy for advanced disease (adjuvant allowed if relapse >6 months later). The key scientific/commercial angle is whether “dual-pathway” PD-1 + angiogenesis blockade in a single molecule can outperform PD-1 alone in pMMR tumors, which are the majority of endometrial cancers and typically less immunogenic; today’s care for this population is carboplatin/paclitaxel plus an immune checkpoint inhibitor with continuation maintenance, with later-line options commonly including lenvatinib + pembrolizumab and other systemic therapies depending on prior exposure and biomarkers.