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

Sponsor

Prelude Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05665530

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Aggressive B-Cell Non-Hodgkin's Lymphoma Aggressive B-Cell NHL Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Mantle Cell Lymphoma (MCL) Richter's Syndrome	Drug: PRT2527	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

51 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Dose limiting toxicity (DLT) of PRT2527 [Baseline through Day 21]
Dose limiting toxicities will be evaluated over the 21-day observation period
Safety and tolerability of PRT2527: AEs, CTCAE Assessments [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)
Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT2527 [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

Anti-tumor activity of PRT2527: Objective response rate (ORR) [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
Anti-tumor activity of PRT2527: Duration of response/Complete Response (DOR/DoCR) [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
Pharmacokinetic profile of PRT2527: Maximum observed plasma concentration [Baseline through approximately 2 years]
PRT2527 pharmacokinetics will be calculated including the maximum observed plasma concentration (Cmax)
Pharmacokinetic profile of PRT2527: Area under the curve [Baseline through approximately 2 years]
PRT2527 pharmacokinetics will be calculated including the area under the plasma concentration versus time curve (AUC)
Pharmacokinetic profile of PRT2527: Time of maximum concentration [Baseline through approximately 2 years]
PRT2527 pharmacokinetics will be calculated including the time of maximum concentration (Tmax)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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 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