THE-630

THE-630 is an investigational small molecule, oral pan-variant inhibitor of the proto-oncogene protein c-kit (KIT), a receptor tyrosine kinase. It was developed for the treatment of advanced gastrointestinal stromal tumors (GIST), particularly in patients who have developed resistance to prior KIT-targeted therapies due to secondary mutations. The drug demonstrated potent activity against a broad range of activating and resistance mutations in KIT, including those in exons 9, 11, 13/14, and 17/18. Despite promising preclinical and early clinical data showing efficacy and manageable safety at lower doses, development was discontinued during phase I/II trials due to dose-limiting toxicities—primarily hand-foot skin reaction—at higher exposures. THE-630 received orphan drug designation from the FDA for GIST but is no longer being pursued following termination of its clinical program[3][4][5][6][8].