ASC2ESCALATE: Asciminib STAMP inhibitor clears BCR-ABL1 ≤ 1% in 83% after one prior TKI

Asciminib, an allosteric BCR-ABL1 “STAMP” inhibitor, was tested in the single-arm Phase 2 ASC2ESCALATE trial (NCT05384587) in 101 adults with chronic-phase CML who had failed or were intolerant to exactly one TKI. Patients received 80 mg QD asciminib with protocol-driven dose-escalation. At Week 24, 82.5% (52/63) achieved early molecular control (BCR::ABL1IS ≤ 1%) and 44.4% reached major molecular response (MMR); Deep molecular response rates like MR4 and MR4.5 rates were 25% and 9.5%, respectively. Headache (22.8%) and nausea (20.8%) were the only all-grade AEs ≥20%, while Grade ≥3 hypertension (8.9%), thrombocytopenia (6.9%) and neutropenia (5.9%) comprised the chief severe toxicities; just 4% discontinued therapy and no arterial-occlusive events occurred. Real-world second-line dasatinib or nilotinib achieve ~31% MMR at 6 months and 47–38% at 12 months—generally with more effusions—so asciminib is matching or beating depth of response earlier and with a better safety profile.