Phase 2 KQB198 + imatinib tests EGFR-targeted protein degrader in 1L metastatic GIST.

This Phase 2, multicenter, open-label study sponsored by Kumquat Biosciences evaluates KQB198 plus imatinib in participants with unresectable or metastatic gastrointestinal stromal tumor (GIST) receiving first-line therapy and harboring KIT or PDGFRA alterations. KQB198 is described by the sponsor as an EGFR-directed protein degrader (a targeted “destroy-the-protein” approach rather than simple kinase inhibition), while imatinib (Novartis) is a small-molecule tyrosine kinase inhibitor that blocks KIT and PDGFRA (and BCR-ABL) signaling that drives most GIST. The primary goals are to characterize safety/tolerability and pharmacokinetics while estimating preliminary efficacy for the combination in the front-line setting. A key scientific/commercial angle is whether adding a degrader can deepen or prolong response on top of imatinib’s established first-line benefit in KIT/PDGFRA-driven disease, potentially delaying emergence of resistant clones. Today’s care for advanced KIT/PDGFRA-mutant GIST typically starts with imatinib, then moves to sequential TKIs such as sunitinib and regorafenib and later agents (including ripretinib), with avapritinib used for PDGFRA exon 18–mutant disease in many settings.