Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study

作者：Jian Li, Xinhua Zhang, Yanhong Deng, Xin Wu, Zhichao Zheng, Yongjian Zhou, Shirong Cai, Yanqiao Zhang, Jun Zhang, Kaixiong Tao, Yuehong Cui, Hui Cao, Kuntang Shen, Jiren Yu, Ye Zhou, Wenxiao Ren, Chenglin Qu, Wanqi Zhao, Jin Hu, Wei Wang, Jason Yang, Lin Shen · 发表于：The Oncologist · 年份：2022 · DOI：10.1093/oncolo/oyac242 · 被引用次数：14 · 研究领域：Gastrointestinal Tumor Research and Treatment、IgG4-Related and Inflammatory Diseases、Gastrointestinal Bleeding Diagnosis and Treatment

BACKGROUND: Avapritinib is a type 1 kinase inhibitor designed to potently and selectively inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation. This multicenter, single-arm, open-label, phase I/II bridging study of NAVIGATOR in Chinese patients evaluated the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST). METHODS: Phase I comprised dose escalation for safety and phase II dose determination. Phase II comprised dose expansion for safety/efficacy evaluations in patients with PDGFRA D842V mutations or patients having received at least 3 lines of therapy without PDGFRA D842V mutations. The primary endpoints were recommended phase II dose, safety, and Independent Radiology Review Committee (IRRC)-assessed objective response rate (ORR). RESULTS: No dose-limiting toxicities occurred (n = 10); the recommended phase II dose was avapritinib 300 mg once daily orally. Fifty-nine patients initially received avapritinib 300 mg. Common grade ≥3 treatment-related adverse events were anemia, decreased white blood cell count, increased blood bilirubin levels, and decreased neutrophil count. In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or l...