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Ivonescimab + enfortumab vedotin (also referred to as ivonescimab + RP3D, where RP3D represents the recommended Phase III dose of ivonescimab combined with enfortumab vedotin) is an investigational combination regimen being developed by Summit Therapeutics for the treatment of genitourinary malignancies, specifically urothelial carcinoma (bladder cancer). Ivonescimab (SMT112) is a potential first-in-class tetravalent bispecific antibody that simultaneously targets programmed cell death protein 1 (PD-1) and vascular endothelial growth factor A (VEGF-A), combining immune checkpoint inhibition with antiangiogenic activity. Enfortumab vedotin (Padcev) is an antibody-drug conjugate (ADC) targeting Nectin-4, which delivers the microtubule-disrupting agent monomethyl auristatin E (MMAE) directly to tumor cells. The combination is being evaluated in the global, multi-regional Phase II/III HARMONi-GU1 trial as a first-line therapy for patients with previously untreated locally advanced or metastatic urothelial carcinoma, comparing its efficacy and safety against the standard of care regimen of pembrolizumab plus enfortumab vedotin.
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