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

Primary Purpose

Aggressive B-Cell Non-Hodgkin's Lymphoma, Aggressive B-Cell NHL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PRT2527
Zanubrutinib
Sponsored by
Prelude Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aggressive B-Cell Non-Hodgkin's Lymphoma focused on measuring Aggressive B-Cell Non-Hodgkin's Lymphoma, Aggressive B-Cell NHL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, CDK9, CLL/SLL, Cyclin-Dependent Kinase 9, Hematologic Malignancies, Mantle Cell Lymphoma (MCL), PRT2527, Relapse/Refractory, Richter's Syndrome, T-cell Lymphoma (TCL), Zanubrutinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of HopeRecruiting
  • American Oncology Partners of Maryland, PARecruiting
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone HealthRecruiting
  • Austin HealthRecruiting
  • Alfred HealthRecruiting
  • Monash HealthRecruiting
  • Linear Clinical Research LtdRecruiting
  • Jewish General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

PRT2527 Monotherapy

PRT2527/Zanubrutinib Combination

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Dose limiting toxicity (DLT) of PRT2527
Dose limiting toxicities will be evaluated over the 21-day observation period for monotherapy and 35-day observation period for combination therapy.
Safety and tolerability of PRT2527 monotherapy and in combination with zanubrutinib: 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)
Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT2527 monotherapy and in combination with zanubrutinib
The MTD/RP2D will be established for further investigation in participants with relapsed or refractory hematologic malignancies

Secondary Outcome Measures

Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: Objective response rate (ORR)
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
Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: Duration of response/Complete Response (DOR/DoCR)
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
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Maximum observed plasma concentration
PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration (Cmax)
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Area under the curve
PRT2527 pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Time of maximum concentration
PRT2527 pharmacokinetics will be calculated including the time of maximum concentration (Tmax)

Full Information

First Posted
December 16, 2022
Last Updated
September 29, 2023
Sponsor
Prelude Therapeutics
Collaborators
BeiGene
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1. Study Identification

Unique Protocol Identification Number
NCT05665530
Brief Title
A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib in Participants With R/R Hematologic Malignancies
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 12, 2023 (Actual)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
April 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prelude Therapeutics
Collaborators
BeiGene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aggressive B-Cell Non-Hodgkin's Lymphoma, Aggressive B-Cell NHL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Mantle Cell Lymphoma (MCL), Richter's Syndrome, T-cell Lymphoma
Keywords
Aggressive B-Cell Non-Hodgkin's Lymphoma, Aggressive B-Cell NHL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, CDK9, CLL/SLL, Cyclin-Dependent Kinase 9, Hematologic Malignancies, Mantle Cell Lymphoma (MCL), PRT2527, Relapse/Refractory, Richter's Syndrome, T-cell Lymphoma (TCL), Zanubrutinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PRT2527 Monotherapy
Arm Type
Experimental
Arm Description
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.
Arm Title
PRT2527/Zanubrutinib Combination
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PRT2527
Intervention Description
PRT2527 will be administered by intravenous infusion once weekly.
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Intervention Description
Zanubrutinib will be provided in capsules for oral administration once daily.
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT) of PRT2527
Description
Dose limiting toxicities will be evaluated over the 21-day observation period for monotherapy and 35-day observation period for combination therapy.
Time Frame
Baseline through Day 21 for monotherapy, and baseline through Day 35 for combination therapy.
Title
Safety and tolerability of PRT2527 monotherapy and in combination with zanubrutinib: AEs, CTCAE Assessments
Description
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)
Time Frame
Baseline through approximately 2 years
Title
Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT2527 monotherapy and in combination with zanubrutinib
Description
The MTD/RP2D will be established for further investigation in participants with relapsed or refractory hematologic malignancies
Time Frame
Baseline through approximately 2 years
Secondary Outcome Measure Information:
Title
Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: Objective response rate (ORR)
Description
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
Time Frame
Baseline through approximately 2 years
Title
Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: Duration of response/Complete Response (DOR/DoCR)
Description
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
Time Frame
Baseline through approximately 2 years
Title
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Maximum observed plasma concentration
Description
PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration (Cmax)
Time Frame
Baseline through approximately 2 years
Title
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Area under the curve
Description
PRT2527 pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
Time Frame
Baseline through approximately 2 years
Title
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Time of maximum concentration
Description
PRT2527 pharmacokinetics will be calculated including the time of maximum concentration (Tmax)
Time Frame
Baseline through approximately 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Contact (Please Do Not Disclose Personal Information)
Phone
See Email
Email
PRT2527-02IVStudy@preludetx.com
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
American Oncology Partners of Maryland, PA
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Individual Site Status
Recruiting
Facility Name
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Name
Alfred Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Name
Monash Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Name
Linear Clinical Research Ltd
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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