Velzatinib (IDRX-42) selective KIT inhibitor drives 61% ORR in 1L GIST; 13.7-mo mPFS in 2L

Velzatinib (IDRX-42; subject to USAN approval) is a next-gen, selective KIT inhibitor designed for broad coverage across primary KIT exons 9/11 and common secondary resistance mutations (exons 13/14 ATP-binding pocket; exons 17/18 activation loop). In the Phase 1/1b StrateGIST 1 study (NCT05489237), velzatinib at the RP1bD (300-mg tablet or exposure-equivalent 400-mg capsule) showed in 2L advanced GIST (n=46) a mPFS of 13.7 months (mFU 14.7 months) with ORR 35% (2 CR, 14 PR) and mutation-subset ORRs ranging from 21% (2L exon 11 only; n=14) to 62% (2L exon 9 only; n=8). In 1L (n=18; mFU 6.4 months), 18/18 had tumor volume reduction and 11/18 (61%) had unconfirmed responses (1 CR, 10 PR); tolerability looked favorable with dose reductions 0% (1L) and 6% (2L), and AE-driven withdrawals 0% (1L) and 4% (2L)—benchmarks to beat remain imatinib in 1L (typical ORR 40–55% and mPFS ~18–24 months) and sunitinib in 2L (mPFS ~6–8 months, low ORR).