Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma.
Обработка статьи · этапы, ошибки и управление
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.
Eigentler Thomas, Thomas Ioannis, Samoylenko Igor, Erdmann Michael, Heinzerling Lucie, Ochsenreither Sebastian, Krauss Jürgen, Oberoi Arjun, Robert Caroline, Lebbe Celeste, Martin-Liberal Juan, Koch Lukas, Richtig Erika, Terheyden Patrick, Weishaupt Carsten, Mohr Peter, Semiletova Yulia, Perez Casilda Llacer, Brossart Peter, Bauernfeind Franz Georg, Fluck Michael, Poltoratskiy Artem, Sekacheva Marina, Soria Ainara, Schmitt-Bormann Beate, Gonzalez Marina, Heß Jana, Wengenmayer Peter, Seibel Tobias, Koch Sven D, Quintini Gianluca, Codó Paula, Falk Martin, Schönborn-Kellenberger Oliver, Gnad-Vogt Ulrike
Аннотация
METHODS: This open-label, cohort-based, phase I dose escalation study aimed to establish the maximum tolerated dose (MTD), recommended dose (RD), safety and preliminary efficacy of CV8102 as monotherapy or in combination with a PD-1 inhibitor. The preliminary efficacy of the RD was assessed in patients with cMEL in the expansion cohorts.
RESULTS: Between September 2017 and October 2022, 98 patients were enrolled in monotherapy and combination therapy dose escalation and dose expansion cohorts. Two patients in the CV8102 monotherapy dose escalation cohort experienced relevant toxicities at the 900 µg dose level. One patient had Grade 3 aspartate transaminase/alanine aminotransferase elevation which met dose-limiting toxicity (DLT) criteria. Another patient experienced Grade 3 immune-mediated pneumonitis. No DLTs occurred in the combination therapy dose escalation cohort. The MTD was not formally reached and the RD for expansion was 600 µg. Common treatment-emergent adverse events were fever (57%), chills (37%) and fatigue (25%). In the dose escalation part, objective responses occurred in 3/33 patients treated with CV8102 as monotherapy and in 2/25 patients treated with CV8102 plus a PD-1 inhibitor. In the expansion cohorts in patients with anti-PD-1 therapy-refractory melanoma, 0/10 patients treated with CV8102 as monotherapy and 5/30 patients (17%) treated in combination with a PD-1 inhibitor experienced objective responses.
CONCLUSIONS: IT CV8102 was generally well tolerated with preliminary signs of efficacy as monotherapy and in combination with a PD-1 inhibitor.
TRIAL REGISTRATION NUMBER: NCT03291002.