Asciminib (STAMP/ABL myristoyl-pocket inhibitor) posts ~39% Week-48 MMR in ≥3L CML-CP optimization study

Asciminib (Scemblix) is a first-in-class STAMP inhibitor that allosterically targets the ABL1 myristoyl pocket (vs ATP-competitive TKIs), evaluated in the non-comparative Phase 3b ASC4OPT study (NCT04948333) in CML-CP after ≥2 prior TKIs with ELN 2020 “warning/failure” response or intolerance; 169 patients were enrolled (including an efficacy population not in MMR at baseline). In patients not in MMR at baseline, MMR was 39.4% at Week 48 (40mg BID 43.4%; 80mg QD 35.4%) and 43.6% at Week 96 (45.8% vs 41.5%); among those dose-escalated to 200mg QD (n=40), 17.5% were in MMR at Week 96, while patients already in MMR at baseline largely maintained MMR through Week 48/96 (93.3%/86.7%). With no randomized comparator here, a pragmatic benchmark is ASCEMBL (≥2 prior TKIs), where asciminib 40mg BID achieved MMR 29.3% at Week 48 and 37.6% at Week 96 (vs bosutinib 15.8% at Week 96), putting ASC4OPT’s Week-48/96 MMR in the same ballpark-to-higher range; safety was reported as consistent with prior asciminib experience (no new signal described).