Dose escalation part of a multinational phase 1-2 study of zelenectide pevedotin for advanced solid tumors

Zelenectide pevedotin (BT8009) is a Bicyle Drug Conjugate comprising a highly selective nectin-4-targeting Bicycle peptide, linked to monomethyl auristatin E. The multinational phase 1-2 Duravelo-1 study evaluates zelenectide pevedotin in adult patients with advanced solid tumors associated with nectin-4 expression. Results from the monotherapy dose escalation part have been published. Patients received zelenectide pevedotin intravenously at 2.5, 5.0 or 7.5 mg/m² once weekly on a 28-day cycle; or 7.5 mg/m² on days 1 and 8 of a 21-day cycle; or 7.5 or 10.0 mg/m² once every 2 weeks on a 28-day cycle. Primary endpoints were safety and tolerability. The dose-escalation part included 49 patients, most with urothelial carcinoma (UC; 25 of 49) who received a median of three previous lines of therapy. Common treatment-related adverse events were nausea (49%; grade 3-4 2%), fatigue (39%; 6%), peripheral neuropathy (33%; 2%), neutropenia (22%; 16%), and skin reactions (22%; 2%). The maximum tolerated dose was 7.5 mg/m² once every 2 weeks. Across doses and tumor types the objective response rate and clinical benefit rate were 24% and 48%, respectively. Among patients with UC, the ORR was 38% and the CBR was 57%. The median duration of response among all patients was 11.1 months. The authors conclude that zelenectide pevedotin monotherapy demonstrate a generally wll-tolerated safety profile and preliminary efficacy, particularly in UC.