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A phase 1b study of the allosteric extracellular FGFR2 inhibitor alofanib in patients with pretreated advanced gastric cancerстатья
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 февраля 2024 г.
- Авторы: Tsimafeyeu Ilya, Statsenko Galina, Vladimirova Liubov, Besova Natalia, Artamonova Elena, Raskin Grigory, Rykov Ivan, Mochalova Anastasia, Utyashev Igor, Gorbacheva Svetlana, Kazey Vasily, Gavrilova Evgenia, Dragun Nadezhda, Moiseyenko Vladimir, Tjulandin Sergei
- Журнал: Investigational New Drugs
- Том: 41
- Номер: 2
- Год издания: 2023
- Издательство: Springer Nature
- Местоположение издательства: Switzerland
- Первая страница: 324
- Последняя страница: 332
- DOI: 10.1007/s10637-023-01340-z
- Аннотация: Alofanib is a small-molecule allosteric extracellular FGFR2 inhibitor. We report safety and preliminary efficacy from the first-in-human phase 1b study of alofanib in heavily pretreated patients with advanced gastric cancer. The standard dose-escalation design 3+3 aimed to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Alofanib was administered daily intravenously 5 days on, 2 days off. There were five dose levels (50-350 mg/m2). All patients received alofanib until disease progression or unacceptable toxicity. 21 patients were enrolled. Patients were predominantly male (71%), 67% had 2 and more metastatic sites, including liver metastases (43%), 19% had ECOG PS 2, and were heavily pretreated (86% had previous 2 and more treatment lines). During dose escalation, no dose-limiting toxicities were observed, and MTD was not defined. 15 (71.4%) patients had at least one adverse event associated with the treatment (TRAE). Grade 3 or higher TRAEs were observed in 6 patients (28.6%). The most common TRAEs included reactions immediately after administration, diarrhea, thrombocytopenia, arthralgia, and headache. The median progression-free survival and overall survival was 3.63 (95% CI 1.58–5.68) and 7.0 (95% CI 3.82–10.18) months, respectively. The 6- and 12-month overall survival rates were 57.1% and 33.3%. Disease control rate was 68% with one durable partial response. The MTD has not been reached and dose of 350 mg/m2, 5 days on, 2 days off has been declared as RP2D. Alofanib showed acceptable tolerability and preliminary signs of clinical activity in the late-line treatment of metastatic gastric cancer. (ClinicalTrials.gov identifier: NCT04071184).
- Добавил в систему: Владимирова Любовь Юрьевна