Mesutoclax (ICP-248), a selective BCL-2 inhibitor, drives 86% cCR with azacitidine in treatment-naïve AML

Mesutoclax (ICP-248) is a next-gen, highly selective BCL-2 inhibitor (positioned as a venetoclax-like backbone with a “cleaner” PK profile) tested with azacitidine in the ongoing global Phase 1 ICP-CL-01205 dose-escalation/expansion trial (NCT06656494) in AML/MDS. As of January 12, 2026, 59 patients were enrolled (8 R/R AML, 39 treatment-naïve [TN] AML, 12 TN MDS); in evaluable TN AML (n=35), cCR (CR+CRi) was 85.7% with centrally assessed CR 65.7%, MRD negativity among cCR responders 86.7%, 3-month DOR rate 91.7%, and 6-month OS 94.1%—numerically above the classic venetoclax+AZA VIALE-A benchmark (cCR 66.4%; mOS 14.7 months), though cross-trial comparisons are fragile and follow-up here is short. No DLTs or tumor lysis syndrome were reported; Grade ≥3 cytopenias were common (neutrophils 62.7%, platelets 50.8%, anemia 33.9%), Grade ≥3 infection was 16.9%, febrile neutropenia 5.1%, and there were no TEAEs leading to discontinuation; count recovery looked slow in TN AML (median 39 days between cycle 1→2 with the protocol’s ANC/platelet thresholds), which may matter operationally versus venetoclax-based practice patterns.