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

PHASE1RECRUITING

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.

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Study details:

This is an open-label, multi-center, dose-escalation, Phase 1 study of PRT2527, a CDK9 inhibitor, as monotherapy for participants with relapsed and refractory lymphoid and myeloid malignancies, in combination with zanubrutinib, a Bruton tyrosine kinase inhibitor (BTKi) for participants with lymphoid malignancies, or in combination with venetoclax, a B-cell lymphoma 2 inhibitor (BCL-2i) in participants with myeloid malignancies. 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 or venetoclax 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 274 participants will be enrolled in the dose escalation and indication-specific, dose confirmation cohorts.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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, 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%

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

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2023-09-12

Primary completion: 2025-11-01

Study completion finish: 2026-03-01

Study type

TREATMENT

Phase

PHASE1

Trial ID

NCT05665530

Intervention or treatment

DRUG: PRT2527

DRUG: Zanubrutinib

DRUG: Venetoclax

Conditions

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

Image related to Aggressive B-Cell Non-Hodgkin's Lymphoma (NHL)

Condition: Aggressive B-Cell Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and more
DRUG: PRT2527 and other drugs
Heidelberg, Victoria, Australia and more
Sponsor: Prelude Therapeutics

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Austin Health

Research sites nearby

Select from list below to view details:

Austin Health
Heidelberg, Victoria, Australia
Alfred Health
Melbourne, Victoria, Australia
Monash Health
Melbourne, Victoria, Australia
Linear Clinical Research Ltd
Perth, Western Australia, Australia

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?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: PRT2527 Monotherapy in Lymphoid Malignancies 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 will be administered by intravenous infusion once weekly.
EXPERIMENTAL: PRT2527/Zanubrutinib Combination in Lymphoid Malignancies 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 PRT2527 will be administered by intravenous infusion once weekly.
EXPERIMENTAL: PRT2527 Monotherapy in Myeloid Malignancies 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 will be administered by intravenous infusion once weekly.
EXPERIMENTAL: PRT2527/Venetoclax Combination in Myeloid Malignancies 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 PRT2527 will be administered by intravenous infusion once weekly.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Anti-tumor activity of PRT2527 as monotherapy and in combination with zanubrutinib or venetoclax: Objective response rate (ORR)	Best overall response 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 or venetoclax: Duration of response/Complete Response (DOR/DoCR)	Duration from time of first observed response 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 or venetoclax: Maximum observed plasma concentration	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 or venetoclax: Area under the curve	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 or venetoclax: Time of maximum concentration	PRT2527 pharmacokinetics will be calculated including the time of maximum concentration (Tmax)	Baseline through approximately 2 years

Frequently Asked Questions

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You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

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