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A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03886831
Recruitment Status : Active, not recruiting
First Posted : March 22, 2019
Last Update Posted : May 5, 2022
Sponsor:
Information provided by (Responsible Party):
Prelude Therapeutics

Study Description
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Brief Summary:
This is a Phase 1 cohort, dose-escalation, dose-expansion study of PRT543 in patients with advanced cancers who have exhausted available treatment options. The purpose of this study is to define a safe dose and schedule to be used in subsequent development of PRT543.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Advanced Solid Tumors Relapsed/Refractory Diffuse Large B-cell Lymphoma Relapsed/Refractory Myelodysplasia Relapsed/Refractory Myelofibrosis Adenoid Cystic Carcinoma Relapsed/Refractory Mantle Cell Lymphoma Relapsed/Refractory Acute Myeloid Leukemia Refractory Chronic Myelomonocytic Leukemia Drug: PRT543 Phase 1

Detailed Description:
This is a multicenter, open-label, sequential-cohort, dose-escalation, dose-expansion Phase 1 study of PRT543 in patients with advanced cancers who have exhausted available treatment options. Enrollment will take place concurrently into two distinct patient groups (one for solid tumors/lymphomas and one for hematological malignancies). The study will consist of 2 parts, a dose escalation part, and once the recommended phase 2 dose (RP2D) has been determined, a cohort expansion part involving up to ten separate cohorts. For patients, the study will include a screening phase, a treatment phase, and a post treatment follow-up phase. An end-of-study visit will be conducted within 30 days after the last dose of PRT543.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 227 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Dose Escalation, Dose Expansion Study of PRT543 in Patients With Advanced Solid Tumors and Hematologic Malignancies
Actual Study Start Date : February 11, 2019
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : December 31, 2022

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Arms and Interventions
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Arm Intervention/treatment
Experimental: PRT543
PRT543 will be administered orally
 Drug: PRT543
PRT543 will be administered orally


Outcome Measures
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Primary Outcome Measures :
  1. To describe dose limiting toxicities (DLT) of PRT543 [ Time Frame: Baseline through Day 28. ]
    Dose limiting toxicities (DLTs) will be evaluated during the first cycle

  2. To determine the maximally tolerated dose (MTD) [ Time Frame: Baseline through approximately 2 years. ]
    The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments.

  3. To determine the recommended phase 2 dose (RP2D) and schedule of PRT543 [ Time Frame: Baseline through approximately 2 years. ]
    The recommended phase 2 dose (RP2D) and optimal dosing schedule of PRT543 will be established for further investigation in participants with advanced malignancies who have failed prior treatments.


Secondary Outcome Measures :
  1. To describe the adverse event profile and tolerability of PRT543 [ Time Frame: Baseline through approximately 2 years ]
    Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy

  2. To determine the maximum observed plasma concentration (Cmax) of PRT543 [ Time Frame: Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. ]
    PRT543 pharmacokinetics will be calculated including the maximum observed plasma concentration.

  3. To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543 [ Time Frame: Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. ]
    PRT543 pharmacokinetics will be calculated including the time to reach maximum observed plasma concentration


Other Outcome Measures:
  1. To determine the terminal elimination half-life (t1/2) of PRT543. [ Time Frame: Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. ]
    PRT543 pharmacokinetics will be calculated including the terminal elimination half life

  2. To determine the area under the plasma concentration versus time curve (AUC) of PRT543 [ Time Frame: Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. ]
    PRT543 pharmacokinetics will be calculated including area under the plasma concentration versus time curve.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
  • Biomarker-selected solid tumors
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
  • Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
  • Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial

Exclusion Criteria:

  • Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases
  • Requirement of pharmacologic doses of glucocorticoids
  • Prior treatment with chimeric antigen receptor T cells (CAR-T cells)
  • HIV positive; known active hepatitis B or C
  • Known hypersensitivity to any of the components of PRT543
  • Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03886831


Locations
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Sponsors and Collaborators
Prelude Therapeutics
More Information
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Responsible Party: Prelude Therapeutics
ClinicalTrials.gov Identifier: NCT03886831    
Other Study ID Numbers: PRT543-01
First Posted: March 22, 2019    Key Record Dates
Last Update Posted: May 5, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prelude Therapeutics:
PRMT5
PRMT5 Inhibitor
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Carcinoma, Adenoid Cystic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Site
Myelodysplastic-Myeloproliferative Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial