SGNDV-001: disitamab vedotin with pembrolizumab in HER2-expressing locally advanced or metastatic urothelial carcinoma.

Introduction: Platinum-based chemotherapy for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC), has been the first-line standard of care for many decades. Enfortumab vedotin, an antibody-drug conjugate, combined with pembrolizumab, a programmed death 1 (PD-1) inhibitor, recently demonstrated improved efficacy versus chemotherapy in la/mUC. Since 60%-80% of patients with UC have tumors expressing human epidermal growth factor receptor 2 (HER2), HER2-directed vedotin-based antibody-drug conjugates may also be beneficial in la/mUC.

Patients and methods: The phase 3 trial SGNDV-001 (C5731001; NCT05911295) is evaluating disitamab vedotin (HER2-directed antibody-drug conjugate) with pembrolizumab compared with chemotherapy in treatment-naive patients with HER2-expressing la/mUC. Dual primary endpoints are progression-free survival (per blinded independent central review) and overall survival. Potential synergistic effects of disitamab vedotin and pembrolizumab could establish this combination as a novel therapeutic option for HER2-expressing la/mUC.