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A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib or Venetoclax in Participants With R/R 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 or venetoclax.
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
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
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
| DRUG: PRT2527
|
EXPERIMENTAL: PRT2527/Zanubrutinib Combination in Lymphoid Malignancies
| DRUG: PRT2527
|
EXPERIMENTAL: PRT2527 Monotherapy in Myeloid Malignancies
| DRUG: PRT2527
|
EXPERIMENTAL: PRT2527/Venetoclax Combination in Myeloid Malignancies
| DRUG: PRT2527
|
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 |
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