NCT05665530

A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib or Venetoclax in Participants With R/R Hematologic Malignancies

A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib or Venetoclax in Participants With Relapsed/Refractory Hematologic Malignancies

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 86 (actual)
• Sponsor: Prelude Therapeutics · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1 dose-escalation study of PRT2527, a potent and highly selective cyclin-dependent kinase (CDK) 9 inhibitor, in participants with select relapsed or refractory (R/R) hematologic malignancies. The purpose of this study is to evaluate the safety, tolerability, recommended phase 2 dose (PR2D), and preliminary efficacy of PRT2527 as a monotherapy and in combination with zanubrutinib or venetoclax.

Detailed description

This is an open-label, multi-center, dose-escalation, Phase 1 study of PRT2527, a CDK9 inhibitor, as monotherapy for participants with relapsed and refractory lymphoid and myeloid malignancies, in combination with zanubrutinib, a Bruton tyrosine kinase inhibitor (BTKi) for participants with lymphoid malignancies, or in combination with venetoclax, a B-cell lymphoma 2 inhibitor (BCL-2i) in participants with myeloid malignancies. The study will be conducted in two parts, the dose escalation phase and the dose confirmation phase for both monotherapy and combination therapy. The dose escalation phase will evaluate escalating doses of PRT2527 as a monotherapy and in combination with zanubrutinib or venetoclax until MTD is identified or when the RP2D is determined. The dose confirmation phase will evaluate indication-specific cohorts at the RP2D to confirm the dose. Approximately 274 participants will be enrolled in the dose escalation and indication-specific, dose confirmation cohorts.

Conditions

• Aggressive B-Cell Non-Hodgkin's Lymphoma (NHL)
• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
• Mantle Cell Lymphoma (MCL)
• Richter's Syndrome
• T-cell Lymphoma
• Diffuse Large B-cell Lymphoma (DLBCL)
• Marginal Zone Lymphoma
• Myeloid Malignancies
• Acute Myeloid Leukemia (AML)
• Chronic Myelomonocytic Leukemia (CMML)
• Myelodysplastic Syndrome (MDS)
• MDS/Myeloproliferative Neoplasm (MPN) Overlap Syndrome

Interventions

Type	Name	Description
DRUG	PRT2527	PRT2527 will be administered by intravenous infusion once weekly.
DRUG	Zanubrutinib	Zanubrutinib will be provided in capsules for oral administration once or twice daily.
DRUG	Venetoclax	Venetoclax will be provided in tablet for oral administration once daily

Timeline

• Start date: 2023-09-12
• Primary completion: 2025-06-12
• Completion: 2026-01-21
• First posted: 2022-12-27
• Last updated: 2026-01-26

Locations

24 sites across 10 countries: United States, Australia, Canada, France, Germany, Italy, Poland, South Korea, Switzerland, United Kingdom

Regulatory

• FDA-regulated drug study