Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

Phase 3 Completed 454 enrolled Takeda Takeda Development Center Americas, Inc. · collab

RandomizedParallel-groupOpen-labelTreatment

Summary

The purpose of this study is to determine whether the combination of pevonedistat and azacitidine improves event-free survival (EFS) when compared with single-agent azacitidine. (An event is defined as death or transformation to AML in participants with MDS or CMML, whichever occurs first, and is defined as death in participants with low-blast AML).

Timeline

Start: 2017-11-28
Primary completion: 2021-05-28
Completion: 2024-10-14

Outcome

Missed primary endpoint

registry analysis (superiority test); Azacitidine 75 mg/m^2 vs Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2; p =0.557; Hazard Ratio (HR) 0.968 (95% CI 0.757 to 1.238); Log Rank NCT03268954 ↗

release “The Phase 3 PANTHER study (Pevonedistat-3001) did not achieve pre-defined statistical significance for the primary endpoint of event-free survival (EFS)” takeda.com ↗

Publications

Ades L, Girshova L, Doronin VA, Diez-Campelo M, Valcarcel D, Kambhampati S, Viniou NA, Woszczyk D, De Paz Arias R, Symeonidis A, Anagnostopoulos A, Munhoz EC, Platzbecker U, Santini V, Fram RJ, Yuan Y, Friedlander S, Faller DV, Sekeres MA. Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML. Blood Adv. 2022 Sep 13;6(17):5132-5145. doi: 10.1182/bloodadvances.2022007334.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Azacitidine	Other / unclassified	75 mg/m2	Intravenous
Subject	Pevonedistat	Small molecule	20 mg/m2	Intravenous