Zelenectide pevedotin (BT8009) Nectin‑4 BDC + pembrolizumab delivers ~55–58% ORR in 1L la/mUC (Duravelo‑2 IA)

Zelenectide pevedotin (zele; BT8009) is a Nectin‑4–targeted Bicycle Drug Conjugate (BDC) evaluated with pembrolizumab in the Phase 2/3 Duravelo‑2 trial (NCT06225596; Cohort 1, previously untreated la/mUC; randomized 1:1:1 vs gemcitabine + cisplatin/carboplatin ± avelumab). At 27 weeks’ follow-up, confirmed BICR ORR was 55% (16/29; CR 24%) with zele 5mg/m² D1/8/15 + pembro and 58% (15/26; CR 31%) with zele 6mg/m² D1/8 + pembro (n=30 per zele arm; median zele duration 6.21 months); by comparison, current 1L SOC enfortumab vedotin + pembrolizumab has reported BICR ORR ~67.5% (CR ~30.4%), while historical platinum/gemcitabine control arms have ORR ~44%. Zele-related AEs occurred in 90% (Gr≥3 40%) at 6mg/m² (dose reductions 20%, discontinuations 3%); common Gr≥3 zele-related AEs at 6mg/m² (≥5%) were neutropenia (10%), neutrophil count decreased (7%), and anemia (7%); AECIs at 6mg/m² included peripheral neuropathy 37% (Gr≥3 3%), skin reactions 17% (no Gr≥3), and eye disorders 10% (no Gr≥3), with no zele-related severe skin reactions reported at 6mg/m².