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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT05665530

Studienbeginn:
September 2023

Letztes Update:
29.03.2024

Wirkstoff:
PRT2527, Zanubrutinib

Indikation (Clinical Trials):
Lymphoma, Neoplasms, Lymphoma, Non-Hodgkin, Leukemia, Lymphoid, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, T-Cell, Lymphoma, T-Cell, Peripheral, Hematologic Neoplasms, Lymphoma, B-Cell, Aggression

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Prelude Therapeutics

Collaborator:
BeiGene

Kontakt

Study Contact (Please Do Not Disclose Personal Information)
Kontakt:
Phone: See Email
E-Mail: clinicaltrials@preludetx.com» Kontaktdaten anzeigen

Studienlocations
(3 von 23)

Universitatsklinikum Koln, Klinik I fur lnnere Medizin
50937 Koln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
UC San Diego Moores Cancer Center
92037 La Jolla
United StatesNoch nicht rekrutierend» Google-Maps
American Oncology Partners of Maryland, PA
20817 Bethesda
United StatesRekrutierend» Google-Maps
Dana-Farber Cancer Institute
02215 Boston
United StatesRekrutierend» Google-Maps
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
10016 New York
United StatesRekrutierend» Google-Maps
University of Virginia Comprehensive Cancer Center
22903 Charlottesville
United StatesRekrutierend» Google-Maps
lstituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRST
47014 Meldola
ItalyRekrutierend» Google-Maps
Ospedale Santa Maria delle Croci - AUSL della Romagna
48121 Ravenna
ItalyRekrutierend» Google-Maps
lnje University Busan Paik Hospital
47392 Busan
Korea, Republic ofRekrutierend» Google-Maps
Keimyung_University Dongsan Hospital
42601 Daegu
Korea, Republic ofRekrutierend» Google-Maps
Samsung Medical Center
06351 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Ente Ospedaliero Cantonale (EOC) lstituto Oncologico della Svizzera italiana (IOSl)- Ospedale San Giovanni (ORBV)
6500 Bellinzona
SwitzerlandRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This is an open-label, multi-center, dose-escalation, Phase 1 study of PRT2527, a CDK9

inhibitor, as monotherapy and in combination with zanubrutinib, a Bruton tyrosine kinase

inhibitor (BTKi), evaluating participants with select R/R hematologic malignancies including

aggressive B-cell lymphoma subtypes, mantle cell lymphoma (MCL), and chronic lymphocytic

leukemia (CLL)/small lymphocytic lymphoma (SLL), including Richter's syndrome and T-cell

lymphoma (TCL) subtypes. 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 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 104 participants will be enrolled in the dose escalation and

indication-specific, dose confirmation cohorts.

Ein-/Ausschlusskriterien

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%

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

Studien-Rationale

Primary outcome:

1. Dose limiting toxicity (DLT) of PRT2527 (Time Frame - Baseline through Day 21 for monotherapy, and baseline through Day 35 for combination therapy.):
Dose limiting toxicities will be evaluated over the 21-day observation period for monotherapy and 35-day observation period for combination therapy.

2. Safety and tolerability of PRT2527 monotherapy and in combination with zanubrutinib: 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 monotherapy and in combination with zanubrutinib (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:

1. Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib: 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 monotherapy and in combination with zanubrutinib: 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 monotherapy and in combination with zanubrutinib: 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 monotherapy and in combination with zanubrutinib: 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 monotherapy and in combination with zanubrutinib: Time of maximum concentration (Time Frame - Baseline through approximately 2 years):
PRT2527 pharmacokinetics will be calculated including the time of maximum concentration (Tmax)

Studien-Arme

  • 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.

Geprüfte Regime

  • PRT2527:
    PRT2527 will be administered by intravenous infusion once weekly.
  • Zanubrutinib:
    Zanubrutinib will be provided in capsules for oral administration once daily.

Quelle: ClinicalTrials.gov


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