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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05665530




Registration number
NCT05665530
Ethics application status
Date submitted
16/12/2022
Date registered
27/12/2022
Date last updated
2/05/2024

Titles & IDs
Public title
A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib in Participants With R/R Hematologic Malignancies
Scientific 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
Secondary ID [1] 0 0
PRT2527-02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aggressive B-Cell Non-Hodgkin's Lymphoma 0 0
Aggressive B-Cell NHL 0 0
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 0 0
Mantle Cell Lymphoma (MCL) 0 0
Richter's Syndrome 0 0
T-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PRT2527
Treatment: Drugs - Zanubrutinib

Experimental: PRT2527 Monotherapy - 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.

Experimental: PRT2527/Zanubrutinib Combination - 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.


Treatment: Drugs: PRT2527
PRT2527 will be administered by intravenous infusion once weekly.

Treatment: Drugs: Zanubrutinib
Zanubrutinib will be provided in capsules for oral administration once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicity (DLT) of PRT2527
Timepoint [1] 0 0
Baseline through Day 21 for monotherapy, and baseline through Day 35 for combination therapy.
Primary outcome [2] 0 0
Safety and tolerability of PRT2527 monotherapy and in combination with zanubrutinib: AEs, CTCAE Assessments
Timepoint [2] 0 0
Baseline through approximately 2 years
Primary outcome [3] 0 0
Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT2527 monotherapy and in combination with zanubrutinib
Timepoint [3] 0 0
Baseline through approximately 2 years
Secondary outcome [1] 0 0
Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: Objective response rate (ORR)
Timepoint [1] 0 0
Baseline through approximately 2 years
Secondary outcome [2] 0 0
Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: Duration of response/Complete Response (DOR/DoCR)
Timepoint [2] 0 0
Baseline through approximately 2 years
Secondary outcome [3] 0 0
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Maximum observed plasma concentration
Timepoint [3] 0 0
Baseline through approximately 2 years
Secondary outcome [4] 0 0
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Area under the curve
Timepoint [4] 0 0
Baseline through approximately 2 years
Secondary outcome [5] 0 0
Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib: Time of maximum concentration
Timepoint [5] 0 0
Baseline through approximately 2 years

Eligibility
Key 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%
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2025
Actual
Sample size
Target
104
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Austin Health - Heidelberg
Recruitment hospital [2] 0 0
Alfred Health - Melbourne
Recruitment hospital [3] 0 0
Monash Health - Melbourne
Recruitment hospital [4] 0 0
Linear Clinical Research Ltd - Perth
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3168 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Virginia
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
France
State/province [7] 0 0
Creteil
Country [8] 0 0
France
State/province [8] 0 0
Lille
Country [9] 0 0
France
State/province [9] 0 0
Lyon
Country [10] 0 0
France
State/province [10] 0 0
Saint-Cloud
Country [11] 0 0
Germany
State/province [11] 0 0
North Rhine-Westphalia
Country [12] 0 0
Italy
State/province [12] 0 0
FC
Country [13] 0 0
Italy
State/province [13] 0 0
Bologna
Country [14] 0 0
Italy
State/province [14] 0 0
Ravenna
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Busan
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Daegu
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seoul
Country [18] 0 0
Poland
State/province [18] 0 0
Malopolskie
Country [19] 0 0
Switzerland
State/province [19] 0 0
Ticino
Country [20] 0 0
United Kingdom
State/province [20] 0 0
West Yorkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Prelude Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
BeiGene
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05665530
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact (Please Do Not Disclose Personal Information)
Address 0 0
Country 0 0
Phone 0 0
See Email
Fax 0 0
Email 0 0
clinicaltrials@preludetx.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05665530