eligibility_summary
Adults ≥18, ECOG 0–2, life expectancy ≥3 mo, newly diagnosed HR‑MDS (WHO) with <20% blasts and IPSS‑R ≥3.5, able to give marrow/blood samples, negative pregnancy tests and effective contraception (men/women) through 180 days post‑dose. Exclude: MDS from MPN, prior CD47/SIRPα therapy, other trials, residual malignancy, severe drug allergy, uncontrolled HTN (≥160/100), serious cardiopulmonary disease, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, breastfeeding, or investigator judgment.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2 randomized, double-blind trial in newly diagnosed higher‑risk MDS. Interventions: AK117, an anti‑CD47 monoclonal antibody (immune checkpoint inhibitor) given IV at two dose levels plus azacitidine, versus placebo plus azacitidine (75 mg/m2 SC, days 1–7, every 4 weeks). Mechanisms: AK117 blocks the CD47–SIRPα “don’t‑eat‑me” signal, enhancing macrophage-mediated phagocytosis of malignant myeloid progenitors/blasts. Azacitidine is a hypomethylating nucleoside analog/DNA methyltransferase inhibitor that induces DNA hypomethylation and cytotoxicity and may increase pro‑phagocytic/antigenic signals. Targets: CD47 on MDS cells, SIRPα pathway on macrophages, epigenetic dysregulation in hematopoietic cells.