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

NCT05665530 | Completed Phase 1 FDA Drug

• 1 other identifier: PRT2527-02
• Study Type: interventional
• Target: 86
• Locations: 10 countries
• Sites: 24

Brief 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.

Conditions

Aggressive B-Cell Non-Hodgkin's Lymphoma (NHL); Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL); Richter's Syndrome; Mantle Cell Lymphoma (MCL); 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

Keywords

Aggressive B-Cell Non-Hodgkin's Lymphoma (NHL); Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; CDK9; Cyclin-Dependent Kinase 9; Hematologic Malignancies; Mantle Cell Lymphoma (MCL); PRT2527; Relapse/Refractory; Richter's Syndrome; T-cell Lymphoma (TCL); Zanubrutinib; Diffuse Large B-cell lymphoma (DLBCL); Venetoclax; Marginal Zone Lymphoma (MZL); Myeloid Malignancies; Acute Myeloid Leukemia (AML); Chronic Myelomonocytic Leukemia (CMML); Myelodysplastic Syndrome (MDS); MDS/Myeloproliferative Neoplasm (MPN) Overlap Syndrome

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT) of PRT2527

  Dose limiting toxicities will be evaluated during Cycle 1 depending on the treatment arm and intrapatient ramp-up.

  Baseline through Day 21, 28, or 35 days.

• Safety and tolerability of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: AEs, CTCAE Assessments

  Safety and tolerability will be evaluated by incidence of DLTs, dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

  Baseline through approximately 2 years

• Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax

  The MTD/RP2D will be established for further investigation in participants with relapsed or refractory hematologic malignancies

  Baseline through approximately 2 years

Secondary Outcomes (5)

• Anti-tumor activity of PRT2527 as monotherapy and in combination with zanubrutinib or venetoclax: Objective response rate (ORR)

  Baseline through approximately 2 years

• Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Duration of response/Complete Response (DOR/DoCR)

  Baseline through approximately 2 years

• Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Maximum observed plasma concentration

  Baseline through approximately 2 years

• Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Area under the curve

  Baseline through approximately 2 years

• Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Time of maximum concentration

  Baseline through approximately 2 years

Study Arms (4)

PRT2527 Monotherapy in Lymphoid Malignancies

EXPERIMENTAL

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.

Drug: PRT2527

PRT2527/Zanubrutinib Combination in Lymphoid Malignancies

EXPERIMENTAL

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.

Drug: PRT2527; Drug: Zanubrutinib

PRT2527 Monotherapy in Myeloid Malignancies

EXPERIMENTAL

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.

Drug: PRT2527

PRT2527/Venetoclax Combination in Myeloid Malignancies

EXPERIMENTAL

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.

Drug: PRT2527; Drug: Venetoclax

Interventions

Venetoclax DRUG

Venetoclax will be provided in tablet for oral administration once daily

PRT2527/Venetoclax Combination in Myeloid Malignancies

PRT2527 DRUG

PRT2527 will be administered by intravenous infusion once weekly.

PRT2527 Monotherapy in Lymphoid Malignancies; PRT2527 Monotherapy in Myeloid Malignancies; PRT2527/Venetoclax Combination in Myeloid Malignancies; PRT2527/Zanubrutinib Combination in Lymphoid Malignancies

Zanubrutinib DRUG

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

PRT2527/Zanubrutinib Combination in Lymphoid Malignancies

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Prelude Therapeutics: lead
• BeiGene: collaborator

Study Sites (24)

City of Hope

Duarte, California, 91010, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

Monash Health

Melbourne, Victoria, 3168, Australia

Location

Linear Clinical Research Ltd

Perth, Western Australia, 6009, Australia

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

Claude Huriez Hospital

Lille, 59000, France

Location

Centre Léon Bérard

Lyon, 69373 Cedex 08, France

Location

Institut Curie

Saint-Cloud, 92210, France

Location

Universitatsklinikum Koln, Klinik I fur lnnere Medizin

Cologne, North Rhine-Westphalia, 50937, Germany

Location

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

Meldola, FC, 47014, Italy

Location

IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola

Bologna, 40138, Italy

Location

Ospedale Santa Maria delle Croci - AUSL della Romagna

Ravenna, 48121, Italy

Location

Pratia MCM Krakow

Krakow, Lesser Poland Voivodeship, 30-727, Poland

Location

lnje University Busan Paik Hospital

Busan, 47392, South Korea

Location

Keimyung_University Dongsan Hospital

Daegu, 42601, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Bellinzona, Canton Ticino, 6500, Switzerland

Location

The Leeds Teaching Hospitals NHS Trust, St James University Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell, Marginal Zone; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Hematologic Neoplasms; Recurrence

Interventions

zanubrutinib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Neoplasms by Site

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: December 27, 2022
• Study Start: September 12, 2023
• Primary Completion: June 12, 2025
• Study Completion: January 21, 2026
• Last Updated: January 26, 2026

Record last verified: 2026-01

Locations

GB (1); CA (1); US (5); CH (1); FR (4); AU (4); IT (3); DE (1); KR (3); PL (1)