eligibility_summary
Adults (≥18) with untreated non-APL AML (incl. MDS/MPN ≥10% blasts or MPAL), ELN 2022 adverse-risk, CD123+ blasts, medically fit (TRM ≤13.1), adequate organ function (CrCl ≥60, LVEF ≥45%, bili/AST/ALT within limits), consent/contraception. Prior low-intensity therapy, hydroxyurea/leukapheresis allowed. Exclude: CML blast phase, FLT3-mutated AML, life expectancy <1 yr, uncontrolled infection, severe mAb allergy, pregnancy/breastfeeding, other investigational therapy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1 dose-escalation combining PVEK (pivekimab sunirine, IMGN632), an anti‑CD123 antibody‑drug conjugate, with FLAG‑Ida for newly diagnosed adverse‑risk AML and other high‑grade myeloid neoplasms. PVEK binds IL‑3Rα (CD123) on leukemic blasts and delivers an internalized DNA‑alkylating cytotoxic payload. Co‑agents: G‑CSF (biologic growth factor, primes myeloid blasts/progenitors), fludarabine (purine analog antimetabolite inhibiting DNA polymerase/primase and ribonucleotide reductase), cytarabine/HiDAC (pyrimidine analog inhibiting DNA polymerase, chain termination), and idarubicin (anthracycline DNA intercalator and topoisomerase II inhibitor). Targets: CD123+ AML/myeloid blasts (including stem/progenitor cells). Pathways: CD123 receptor–mediated ADC uptake, DNA replication/repair, topoisomerase II, and G‑CSF–driven myeloid cycling.