An Efficacy and Safety Study of Azacitidine Subcutaneous in Combination With Durvalumab (MEDI4736) in Previously Untreated Adults With Higher-Risk Myelodysplastic Syndromes (MDS) or in Elderly Patients With Acute Myeloid Leukemia (AML)

Summary

The primary objective of this study is to evaluate the efficacy of subcutaneous azacitidine in combination with durvalumab as compared with subcutaneous azacitidine alone in adults with previously untreated, higher risk MDS who are not eligible for HSCT or in adults ≥ 65 years old with previously untreated AML who are not eligible for HSCT, with intermediate or poor cytogenetic risk.

Timeline

Start

2016-06-03

Primary completion

2018-12-31

Completion

2021-12-27

Outcome

Missed primary endpoint

registry analysis (superiority test); MDS: Azacitidine + Durvalumab vs MDS: Azacitidine Alone; p = 0.1838; Wald asymptotic two-sided test NCT02775903 ↗

registry analysis (superiority test); AML: Azacitidine + Durvalumab vs AML: Azacitidine Alone; p = 0.6180; Wald asymptotic two-sided test NCT02775903 ↗

Publications

• Bewersdorf JP, Hasle V, Shallis RM, Thompson E, Lopes de Menezes D, Rose S, Boss I, Mendez L, Podoltsev N, Stahl M, Kewan T, Halene S, Haferlach T, Fox BA, Zeidan AM. Integrated Immune Landscape Analysis of RNA Splicing Factor-Mutant AML and Higher risk MDS Treated with Azacitidine +/- Durvalumab. Ther Adv Hematol. 2025 Jun 21;16:20406207251347344. doi: 10.1177/20406207251347344. eCollection 2025.
• Zeidan AM, Bewersdorf JP, Hasle V, Shallis RM, Thompson E, de Menezes DL, Rose S, Boss I, Halene S, Haferlach T, Fox BA. Integrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine. Ther Adv Hematol. 2024 Jun 15;15:20406207241257904. doi: 10.1177/20406207241257904. eCollection 2024.
• Zeidan AM, Boss I, Beach CL, Copeland WB, Thompson E, Fox BA, Hasle VE, Ogasawara K, Cavenagh J, Silverman LR, Voso MT, Hellmann A, Tormo M, O'Connor T, Previtali A, Rose S, Garcia-Manero G. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes. Blood Adv. 2022 Apr 12;6(7):2207-2218. doi: 10.1182/bloodadvances.2021005487.
• Zeidan AM, Boss I, Beach CL, Copeland WB, Thompson E, Fox BA, Hasle VE, Hellmann A, Taussig DC, Tormo M, Voso MT, Cavenagh J, O'Connor T, Previtali A, Rose S, Silverman LR. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML. Blood Adv. 2022 Apr 12;6(7):2219-2229. doi: 10.1182/bloodadvances.2021006138.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Azacitidine	Other / unclassified	75 mg/m2	Subcutaneous
Subject	Durvalumab	Monoclonal antibody	1500 mg	Intravenous

Indications