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

March 28, 2024 updated by: Prelude Therapeutics

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, multi-center, dose-escalation, Phase 1 study of PRT2527, a CDK9 inhibitor, as monotherapy and in combination with zanubrutinib, a Bruton tyrosine kinase inhibitor (BTKi), evaluating participants with select R/R hematologic malignancies including aggressive B-cell lymphoma subtypes, mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), including Richter's syndrome and T-cell lymphoma (TCL) subtypes. 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 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 104 participants will be enrolled in the dose escalation and indication-specific, dose confirmation cohorts.

Study Type

Interventional

Enrollment (Estimated)

104

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Recruiting
        • Austin Health
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • Alfred Health
      • Melbourne, Victoria, Australia, 3168
        • Recruiting
        • Monash Health
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Recruiting
        • Linear Clinical Research Ltd
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • Jewish General Hospital
  • France
      • Creteil, France, 94010
        • Recruiting
        • Hopital Henri Mondor
      • Lille, France, 59000
        • Recruiting
        • Claude Huriez Hospital
      • Lyon, France, 69373 Cedex 08
        • Recruiting
        • Centre Leon Berard
      • Saint-Cloud, France, 92210
        • Recruiting
        • Institut Curie
  • Germany
    • North Rhine-Westphalia
      • Koln, North Rhine-Westphalia, Germany, 50937
        • Recruiting
        • Universitatsklinikum Koln, Klinik I fur lnnere Medizin
  • Italy
      • Ravenna, Italy, 48121
        • Recruiting
        • Ospedale Santa Maria delle Croci - AUSL della Romagna
    • FC
      • Meldola, FC, Italy, 47014
        • Recruiting
        • lstituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRST
  • Korea, Republic of
      • Busan, Korea, Republic of, 47392
        • Recruiting
        • lnje University Busan Paik Hospital
      • Daegu, Korea, Republic of, 42601
        • Recruiting
        • Keimyung_University Dongsan Hospital
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center
  • Poland
    • Malopolskie
      • Kraków, Malopolskie, Poland, 30-727
        • Recruiting
        • Pratia MCM Krakow
  • Switzerland
    • Ticino
      • Bellinzona, Ticino, Switzerland, 6500
        • Recruiting
        • Ente Ospedaliero Cantonale (EOC) lstituto Oncologico della Svizzera italiana (IOSl)- Ospedale San Giovanni (ORBV)
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
      • La Jolla, California, United States, 92037
        • Not yet recruiting
        • UC San Diego Moores Cancer Center
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Recruiting
        • American Oncology Partners of Maryland, PA
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • Laura and Isaac Perlmutter Cancer Center At Nyu Langone Health
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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, CLL/SLL, including Richter's syndrome, based on local testing , or TCL (monotherapy only) that have relapsed or become refractory to or be ineligible for standard-of-care therapy
  • Must provide either an archival or fresh tumor tissue sample from a core or excisional/surgical biopsy
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • 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
  • Mean corrected QT interval of > 470 msec following triplicate ECG measurements or a history of long QT Syndrome
  • 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 or inducers or use of moderate CYP3A4 inducers (for combination therapy only)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PRT2527 Monotherapy
PRT2527 will be administered by intravenous infusion once weekly on a 21-day treatment cycle 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 will be administered by intravenous infusion once weekly.
Experimental: PRT2527/Zanubrutinib Combination

PRT2527 will be administered by intravenous infusion once weekly on a 35-day treatment cycle for Cycle 1 followed by 21-day treatment for subsequent treatment cycles 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 daily.
Drug: PRT2527
PRT2527 will be administered by intravenous infusion once weekly.
Drug: Zanubrutinib
Zanubrutinib will be provided in capsules for oral administration once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose limiting toxicity (DLT) of PRT2527
Time Frame: Baseline through Day 21 for monotherapy, and baseline through Day 35 for combination therapy.
Dose limiting toxicities will be evaluated over the 21-day observation period for monotherapy and 35-day observation period for combination therapy.
Baseline through Day 21 for monotherapy, and baseline through Day 35 for combination therapy.
Safety and tolerability of PRT2527 monotherapy and in combination with zanubrutinib: AEs, CTCAE Assessments
Time Frame: Baseline through approximately 2 years
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
Time Frame: Baseline through approximately 2 years
The MTD/RP2D will be established for further investigation in participants with relapsed or refractory hematologic malignancies
Baseline through approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: Objective response rate (ORR)
Time Frame: Baseline through approximately 2 years
Best overall response of either complete response (CR) or partial response (PR), as assessed by the investigator in accordance with standard disease-specific criteria for the hematologic malignancies under study
Baseline through approximately 2 years
Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: Duration of response/Complete Response (DOR/DoCR)
Time Frame: Baseline through approximately 2 years
Duration from time of first observed response (CR or PR) to the earliest date of disease progression, as assessed by the investigator in accordance with standard disease-specific criteria for the hematologic malignancies under study, or death due to any cause, whichever occurs first
Baseline through approximately 2 years
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Maximum observed plasma concentration
Time Frame: Baseline through approximately 2 years
PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration (Cmax)
Baseline through approximately 2 years
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Area under the curve
Time Frame: Baseline through approximately 2 years
PRT2527 pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
Baseline through approximately 2 years
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Time of maximum concentration
Time Frame: Baseline through approximately 2 years
PRT2527 pharmacokinetics will be calculated including the time of maximum concentration (Tmax)
Baseline through approximately 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Prelude Therapeutics

Collaborators

BeiGene

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 12, 2023

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

December 16, 2022

First Submitted That Met QC Criteria

December 16, 2022

First Posted (Actual)

December 27, 2022

Study Record Updates

Last Update Posted (Actual)

March 29, 2024

Last Update Submitted That Met QC Criteria

March 28, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRT2527-02

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on T-cell Lymphoma

Clinical Trials on PRT2527

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Albania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe