Phase II basket study of brigatinib for ALK fusion-positive solid tumors: WJOG15221M/ALLBREAK (a decentralized clinical trial design)

Anaplastic lymphoma kinase (ALK) rearrangements, oncogenic drivers found in 3-5% of non-small cell lung cancer (NSCLC), are also detected in 0.2% of other solid tumors with poor prognosis. Brigatinib, a second-generation ALK-tyrosine kinase inhibitor (ALK-TKI), has shown potential efficacy in ALK fusion-positive tumors besides NSCLC, supported by preclinical studies and case reports. The WJOG15221M/ALLBREAK trial was designed to evaluate the safety and efficacy of brigatinib in these rare cancers.This multicenter, open-label, single-arm, phase II basket trial enrolls patients with advanced or recurrent ALK fusion-positive solid tumors who are refractory to or intolerant of standard therapies. By adopting a decentralized clinical trial (DCT) platform, the study allows patients to participate either through on-site visits or video conferencing systems at their nearby hospitals, thereby enhancing accessibility and inclusivity, while facilitating enrollment from diverse locations. ALK fusion genes are identified by next-generation sequencing (NGS) or by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Due to rapid enrollment, the target sample size was expanded to 28 patients. The primary endpoint is objective response rate confirmed by central assessment; secondary endpoints include duration of response, progression-free survival, overall survival, and safety.Clinical trial registration: jRCT2041210148 (https://jrct.mhlw.go.jp).