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

NCT ID: NCT05665530

Last Updated: 2026-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-12

Study Completion Date

2026-01-21

Brief Summary

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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

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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

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PRT2527 Monotherapy in Lymphoid Malignancies

PRT2527 will be administered by intravenous infusion once weekly at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication-specific cohorts during the dose confirmation phase.

Group Type EXPERIMENTAL

PRT2527

Intervention Type DRUG

PRT2527 will be administered by intravenous infusion once weekly.

PRT2527/Zanubrutinib Combination in Lymphoid Malignancies

PRT2527 will be administered by intravenous infusion once weekly at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication specific cohort during the dose confirmation phase.

Zanubrutinib will be administered orally as combination therapy once or twice daily.

Group Type EXPERIMENTAL

PRT2527

Intervention Type DRUG

PRT2527 will be administered by intravenous infusion once weekly.

Zanubrutinib

Intervention Type DRUG

Zanubrutinib will be provided in capsules for oral administration once or twice daily.

PRT2527 Monotherapy in Myeloid Malignancies

PRT2527 will be administered by intravenous infusion once weekly at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication-specific cohorts during the dose confirmation phase.

Group Type EXPERIMENTAL

PRT2527

Intervention Type DRUG

PRT2527 will be administered by intravenous infusion once weekly.

PRT2527/Venetoclax Combination in Myeloid Malignancies

PRT2527 will be administered by intravenous infusion once weekly at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication specific cohort during the dose confirmation phase.

Venetoclax will be administered orally as a combination therapy once daily.

Group Type EXPERIMENTAL

PRT2527

Intervention Type DRUG

PRT2527 will be administered by intravenous infusion once weekly.

Venetoclax

Intervention Type DRUG

Venetoclax will be provided in tablet for oral administration once daily

Interventions

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PRT2527

PRT2527 will be administered by intravenous infusion once weekly.

Intervention Type DRUG

Zanubrutinib

Zanubrutinib will be provided in capsules for oral administration once or twice daily.

Intervention Type DRUG

Venetoclax

Venetoclax will be provided in tablet for oral administration once daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
* Histologically or cytologically confirmed diagnosis of aggressive B-cell lymphoma subtypes, MCL, MZL, or CLL/SLL (including Richter's syndrome) based on local testing, or TCL (monotherapy only), AML, CMML, MDS, or MDS/MPN overlap syndrome that have relapsed or become refractory to or be ineligible for standard-of-care therapy
* Eastern Cooperative Oncology Group (ECOG) Performance Status of \< 2.
* Adequate organ function (hematology, renal, and hepatic)
* Echocardiogram (or multigated acquisition \[MUGA\] scan) indicating a left ventricular ejection fraction of ≥ 50%

Exclusion Criteria

* Have active central nervous system involvement by malignancy, uncontrolled intercurrent illnesses, and active infections requiring systemic therapy
* Have undergone HSCT within the last 90 days or have graft versus host disease (GvHD) Grade \> 1 at study entry
* Have severe pulmonary disease with hypoxemia
* History of another malignancy except for adequately treated non-melanoma skin cancer or lentigo maligna, superficial bladder cancer, and carcinoma in situ of the cervix without evidence of disease, and asymptomatic prostate cancer without known metastatic disease and no requirement for therapy
* Concurrent treatment or within 15 days of starting study treatment with strong CYP3A4 inhibitors
* Prior exposure to a CDK9 inhibitor
* Wait at least 5 half-lives of the agent or 14 days after their investigational or approved therapies before start of study treatment, whichever is shorter
* Mean corrected QT interval of \> 470 msec following triplicate ECG measurement or history of long QT syndrome
* T-Cell leukemias
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeiGene

INDUSTRY

Sponsor Role collaborator

Prelude Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope

Duarte, California, United States

Site Status

American Oncology Partners of Maryland, PA

Bethesda, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

Site Status

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, United States

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Alfred Health

Melbourne, Victoria, Australia

Site Status

Monash Health

Melbourne, Victoria, Australia

Site Status

Linear Clinical Research Ltd

Perth, Western Australia, Australia

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

Claude Huriez Hospital

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Institut Curie

Saint-Cloud, , France

Site Status

Universitatsklinikum Koln, Klinik I fur lnnere Medizin

Cologne, North Rhine-Westphalia, Germany

Site Status

lstituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRST

Meldola, FC, Italy

Site Status

IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola

Bologna, , Italy

Site Status

Ospedale Santa Maria delle Croci - AUSL della Romagna

Ravenna, , Italy

Site Status

Pratia MCM Krakow

Krakow, Lesser Poland Voivodeship, Poland

Site Status

lnje University Busan Paik Hospital

Busan, , South Korea

Site Status

Keimyung_University Dongsan Hospital

Daegu, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Ente Ospedaliero Cantonale (EOC) lstituto Oncologico della Svizzera italiana (IOSl)- Ospedale San Giovanni (ORBV)

Bellinzona, Canton Ticino, Switzerland

Site Status

The Leeds Teaching Hospitals NHS Trust, St James University Hospital

Leeds, West Yorkshire, United Kingdom

Site Status

Countries

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United States Australia Canada France Germany Italy Poland South Korea Switzerland United Kingdom

Other Identifiers

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PRT2527-02

Identifier Type: -

Identifier Source: org_study_id

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