NB003 Broad-Spectrum KIT Inhibitor Delivers ≈43% ORR and 13.8-mo mPFS in 4th-Line GIST

NB003 is an oral tyrosine-kinase inhibitor engineered to hit both ATP-binding–site (ex13/14) and activation-loop (ex17/18) KIT resistance mutations that undercut imatinib and next-gen agents. In the phase 1 escalation/expansion trial (NCT04936178; n = 154 evaluable), adults with KIT-mutant GIST received NB003. Confirmed ORR was 27.3% overall, rising to 40% in third-line and 42.9% in fourth-line settings; median PFS reached 13.8 months in fourth-lineand was not reached in third-line, far exceeding the 9% ORR and 6.3 -mo PFS historically seen with ripretinib in similar patients. Lab-only creatine-kinase rise (80%), cytopenias, and edema were the commonest TRAEs; grade ≥3 GI bleeding occurred in 6%, with a generally manageable safety profile.