Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
First-in-Human, Phase I/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation.
СтатьяКлиническое исследование I фазыКлиническое исследование II фазыМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Baldini Capucine, Verlingue Loic, Goldschmidt Vincent, Doger de Spéville Bernard, Lostes Julia, Italiano Antoine, Cousin Sophie, Falchook Gerald S, Necchi Andrea, Reig Torras Oscar, Fontana Elisa, Carter Louise, Rodon Ahnert Jordi, Brown Jason R, DeMars Leslie R, Josephs Kate, Dickson Amy, Xu Cong, Bader Justin, Campbell Carly, Sharma Rajiv, McKean Meredith
Аннотация
PURPOSE: Zelenectide pevedotin (BT8009) is a Bicycle Drug Conjugate comprising a highly selective Nectin-4-targeting Bicycle peptide, linked to monomethyl auristatin E. We report monotherapy dose-escalation results from Duravelo-1 (Phase I/II; ClinicalTrials.gov identifier: NCT04561362).
METHODS: Adults with advanced/metastatic solid tumors associated with Nectin-4 expression 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 objectives were to evaluate safety and tolerability; antitumor activity and pharmacokinetic characterization were secondary objectives.
RESULTS: Forty-nine patients, most with urothelial carcinoma (UC; 25 of 49), received three previous lines of therapy (median). Common treatment-related adverse events (TRAEs) included nausea (49% [grade 3/4 2%]), likely because of a lack of prophylactic antiemetics during the dose-limiting toxicity period, and fatigue (39% [grade 3/4 6%]). The most common TRAEs of clinical interest were peripheral neuropathy (33% [grade 3/4 2%]), neutropenia (22% [grade 3/4 16%]), and skin reactions (22% [grade 3/4 2%]). The maximum tolerated dose was 7.5 mg/m2 once every 2 weeks; the recommended phase 2 doses were 5.0 mg/m2 once weekly and 7.5 mg/m2 on days 1 and 8 of a 21-day cycle. Across doses (efficacy-evaluable; all tumor types), the objective response rate (ORR) was 24% and the clinical benefit rate (CBR) was 48% (n = 10 of 42; 95% CI, 12.1 to 39.5); the ORR was 38% and the CBR was 57% for patients with UC (n = 8 of 21; 95% CI, 18.1 to 61.6). The median duration of response and the median follow-up for all patients were 11.1 and 7.4 months, respectively.
CONCLUSION: Zelenectide pevedotin monotherapy demonstrated a generally well-tolerated safety profile and preliminary efficacy, particularly in UC, supporting investigation of UC and non-UC populations in the expansion phase.
METHODS: Adults with advanced/metastatic solid tumors associated with Nectin-4 expression 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 objectives were to evaluate safety and tolerability; antitumor activity and pharmacokinetic characterization were secondary objectives.
RESULTS: Forty-nine patients, most with urothelial carcinoma (UC; 25 of 49), received three previous lines of therapy (median). Common treatment-related adverse events (TRAEs) included nausea (49% [grade 3/4 2%]), likely because of a lack of prophylactic antiemetics during the dose-limiting toxicity period, and fatigue (39% [grade 3/4 6%]). The most common TRAEs of clinical interest were peripheral neuropathy (33% [grade 3/4 2%]), neutropenia (22% [grade 3/4 16%]), and skin reactions (22% [grade 3/4 2%]). The maximum tolerated dose was 7.5 mg/m2 once every 2 weeks; the recommended phase 2 doses were 5.0 mg/m2 once weekly and 7.5 mg/m2 on days 1 and 8 of a 21-day cycle. Across doses (efficacy-evaluable; all tumor types), the objective response rate (ORR) was 24% and the clinical benefit rate (CBR) was 48% (n = 10 of 42; 95% CI, 12.1 to 39.5); the ORR was 38% and the CBR was 57% for patients with UC (n = 8 of 21; 95% CI, 18.1 to 61.6). The median duration of response and the median follow-up for all patients were 11.1 and 7.4 months, respectively.
CONCLUSION: Zelenectide pevedotin monotherapy demonstrated a generally well-tolerated safety profile and preliminary efficacy, particularly in UC, supporting investigation of UC and non-UC populations in the expansion phase.