Zelenectide Pevedotin (Nectin-4 BTC) Delivers 50% ORR in NECTIN4-Amplified, Heavily Pretreated TNBC

Zelenectide pevedotin is a low-molecular-weight Bicycle® toxin conjugate that ferries MMAE to Nectin-4; in the Phase 1b DURAVELO-1 dose-expansion (5 mg/m² weekly), 32 triple-negative breast-cancer patients with a median six prior lines were enrolled. Of 19 tumors tested, 6 (32%) carried NECTIN4 gene amplification (FISH ratio ≥ 2.0); this biomarker cohort achieved a 50% objective response rate (3/6) and 100% disease control, versus 7.7% (1/13) in non-amplified disease. Overall ORR was 13.3% (4/30), and grade ≥3 drug-related adverse events occurred in 34% (neutropenia, neuropathy). Notably, all NECTIN4-amp responders had previously progressed on sacituzumab govitecan, whose benchmark ORR is ~35% and median PFS 5.5 mo in similar settings.

https://aacrjournals.org/clincancerres/article/31/12_Supplement/P4-10-21/753923/Abstract-P4-10-21-Enhanced-anti-tumor-activity-of