Phase 2/3 Ivonescimab PD-1×VEGF bispecific antibody plus enfortumab vedotin Nectin-4 ADC in la/mUC

HARMONi-GU1 (NCT07815665) is a randomized, open-label, multicenter Phase 2/3 study testing whether ivonescimab + enfortumab vedotin (EV) can outperform pembrolizumab + EV as first-line therapy for unresectable locally advanced or metastatic urothelial carcinoma. Ivonescimab (Summit Therapeutics; originally from Akeso) is a PD-1 and VEGF-targeting bispecific antibody intended to couple checkpoint blockade with anti-angiogenic signaling suppression, while EV (Astellas/Seagen and Pfizer) is a Nectin-4–directed antibody-drug conjugate that delivers the microtubule toxin MMAE. Phase 2 includes two ivonescimab dose levels with EV to select dosing; Phase 3 uses the recommended Phase 3 dose vs the established control regimen of pembrolizumab (Merck) + EV. The commercial/scientific angle is a direct head-to-head attempt to upgrade today’s widely used frontline standard (EV + PD-1) by swapping in a PD-1×VEGF bispecific, building on the broader thesis that dual PD-(L)1/VEGF targeting can deepen and extend responses versus PD-1 alone.