NCT02936752

Testing the Safety and Efficacy of the Combination of the Antibody Pembrolizumab and Entinostat in Patients With Myelodysplastic Syndrome Who Are Not Responding to Hypomethylating Agents

A Phase 1b Study of the Anti-PD1 Antibody Pembrolizumab in Combination With the Histone Deacetylase Inhibitor, Entinostat for Treatment of Patients With Myelodysplastic Syndromes After DNA Methyltransferase Inhibitor Therapy Failure

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the side effects and best dose of entinostat when given together with pembrolizumab in treating patients with myelodysplastic syndrome after deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi) therapy failure. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving entinostat together with pembrolizumab may work better in treating patients with myelodysplastic syndrome after DNMTi therapy failure.

Detailed description

PRIMARY OBJECTIVE: I. To assess safety, tolerability, and identify the maximum tolerated dose (MTD) of entinostat given in combination with MK-3475 (pembrolizumab). SECONDARY OBJECTIVE: I. To obtain a preliminary estimate of efficacy of entinostat in combination with MK-3475 (pembrolizumab). EXPLORATORY OBJECTIVE: I. To assess the dynamic quantitative change in measurable immunological biomarkers (proportions of myeloid-derived suppressor cells \[MDSCs\], and programmed death protein-1 \[PD-1\] expression in bone marrow) with the combined epigenetic-immunotherapy and correlation with any observed clinical responses. OUTLINE: This is a dose-escalation study of entinostat. Patients receive lower dose entinostat orally (PO) on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab intravenously (IV) over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a stable disease (SD) status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. After completion of study treatment, patients are followed up monthly for 6 months.

Conditions

• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Entinostat	Given PO
BIOLOGICAL	Pembrolizumab	Given IV

Timeline

• Start date: 2017-06-23
• Primary completion: 2022-11-04
• Completion: 2025-02-12
• First posted: 2016-10-18
• Last updated: 2025-03-25
• Results posted: 2024-10-01

Locations

19 sites across 1 country: United States

Regulatory

• FDA-regulated drug study