A Phase 1 Study of Durvalumab As Monotherapy or Combined With Tremelimumab With or Without Azacitidine in Patients With Myelodysplastic Syndrome

Authors

Guillermo Garcia-Manero
Manila Gaddh
Uwe Platzbecker
R Coleman Lindsley
Sarah M Larson
Timothy Chevassut
Pierre Fenaux
Rami Komrokji
Roger Lyons
Aref Al-Kali
Yu Jiang
John Bothos
Danielle M Townsley
Amer M Zeidan

Publication Date

3-1-2025

Journal

Annals of Hematology

Abstract

Upregulation of programmed death ligand-1 (PD-L1) has been observed in patients with MDS, and its expression on myeloblasts is associated with progression to AML. This open-label, phase 1 study evaluated the safety and tolerability of the PD-L1 antibody durvalumab as monotherapy (part 1) and in combination with tremelimumab, with or without azacitidine (part 2), in patients with MDS who progressed following hypomethylating agent treatment. Sixty-seven adults with MDS were enrolled (part 1, 40 with low/intermediate-1 or intermediate-2/high IPSS risk status; part 2, 27 with intermediate-2/high IPSS risk status). Primary safety endpoints included dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). Secondary endpoints included evaluation of clinical outcomes, survival, and pharmacokinetics. Dose-limiting toxicities were experienced by no patients in part 1 and 3 patients (11%) in part 2. The most common treatment-emergent adverse events were diarrhea and fatigue (40% each) in part 1 and fatigue (44%) and anemia (37%) in part 2. In parts 1 and 2, 15% of patients experienced marrow complete response as their best overall response, according to IWG criteria. Hematologic improvement was observed in 35% and 30% of patients respectively in part 1 and part 2. The study was terminated early due to limited efficacy.

Keywords

Humans, Myelodysplastic Syndromes, Antibodies, Monoclonal, Humanized, Female, Male, Aged, Middle Aged, Azacitidine, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, Adult, Acute myeloid leukemia, CTLA-4, Durvalumab, First-in-human, MDS, PD-L1

DOI

10.1007/s00277-024-06081-4

PMID

40153010

PMCID

PMC12031784

PubMedCentral® Posted Date

3-28-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes