History of Changes for Study: NCT05665530

A Study of PR2527 in Participants With Relapsed/Refractory Hematologic Malignancies

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Study Record Versions

Version	Submitted Date	Changes
1	December 16, 2022	None (earliest Version on record)
2	February 6, 2023	Study Status and Study Identification
3	February 21, 2023	Recruitment Status, Study Status, Contacts/Locations and Oversight
4	April 4, 2023	Study Status
5	May 2, 2023	Study Status
6	June 1, 2023	Study Status
7	June 29, 2023	Study Status
8	July 7, 2023	Study Status and Contacts/Locations
9	August 2, 2023	Study Status and Contacts/Locations
10	September 1, 2023	Arms and Interventions, Study Status, Outcome Measures, Study Design, Conditions, Study Description, Study Identification, Contacts/Locations, Eligibility and Sponsor/Collaborators
11	September 14, 2023	Study Status
12	September 29, 2023	Contacts/Locations and Study Status
13	October 27, 2023	Study Status and Contacts/Locations
14	December 1, 2023	Study Status and Contacts/Locations
15	December 14, 2023	Contacts/Locations and Study Status
16	January 30, 2024	Study Status and Contacts/Locations
17	March 1, 2024	Contacts/Locations and Study Status
18	March 28, 2024	Contacts/Locations and Study Status
19	May 1, 2024	Contacts/Locations and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	PRT2527-02
Brief Title:	A Study of PR2527 in Participants With Relapsed/Refractory Hematologic Malignancies
Official Title:	A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT2527 in Participants With Relapsed/Refractory Hematologic Malignancies
Secondary IDs:

Study Status


Record Verification:	December 2022
Overall Status:	Not yet recruiting
Study Start:	March 2023
Primary Completion:	March 2025 [Anticipated]
Study Completion:	March 2025 [Anticipated]

First Submitted:	December 16, 2022
First Submitted that Met QC Criteria:	December 16, 2022
First Posted:	December 27, 2022 [Actual]

Last Update Submitted that Met QC Criteria:	December 16, 2022
Last Update Posted:	December 27, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Prelude Therapeutics
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

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.

Detailed Description:

This is an open-label, multi-center, dose-escalation, Phase 1 study of PRT2527, a CDK9 inhibitor, evaluating participants with select R/R hematologic malignancies including aggressive B-cell lymphoma subtypes, mantle cell lymphoma (MCL), and chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL), including Richter's syndrome. The study will be conducted in two parts, the dose escalation phase and the dose confirmation phase. The dose escalation phase will evaluate escalating doses of PRT2527 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 51 participants will be enrolled in the dose escalation and indication-specific, dose confirmation cohorts.

Conditions


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

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1
Interventional Study Model:	Sequential Assignment
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	51 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: PRT2527 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 on a 21-day treatment cycle

Outcome Measures


Primary Outcome Measures:
1.	Dose limiting toxicity (DLT) of PRT2527 [ Time Frame: Baseline through Day 21 ] Dose limiting toxicities will be evaluated over the 21-day observation period
2.	Safety and tolerability of PRT2527: 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)
3.	Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT2527 [ Time Frame: Baseline through approximately 2 years ] The MTD/RP2D will be established for further investigation in participants with relapsed or refractory hematologic malignancies
Secondary Outcome Measures:
1.	Anti-tumor activity of PRT2527: 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
2.	Anti-tumor activity of PRT2527: 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
3.	Pharmacokinetic profile of PRT2527: Maximum observed plasma concentration [ Time Frame: Baseline through approximately 2 years ] PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration (Cmax)
4.	Pharmacokinetic profile of PRT2527: 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)
5.	Pharmacokinetic profile of PRT2527: Time of maximum concentration [ Time Frame: Baseline through approximately 2 years ] PRT2527 pharmacokinetics will be calculated including the time of maximum concentration (Tmax)

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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 or CLL/SLL, including Richter's syndrome, based on local testing 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 with strong CYP3A4 inhibitors or inducers 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

Contacts/Locations


Central Contact Person:	Study Contact (Please Do Not Disclose Personal Information) Telephone: See Email Email: PRT2527-02IVStudy@preludetx.com
Locations:

IPDSharing


Plan to Share IPD:

References


Citations:
Links:
Available IPD/Information: