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PRT1419 as Monotherapy or in Combination With Azacitidine or Venetoclax in R/R Myeloid or B-cell 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05107856
Recruitment Status : Recruiting
First Posted : November 4, 2021
Last Update Posted : April 4, 2023
Sponsor:
Information provided by (Responsible Party):
Prelude Therapeutics

Study Description
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Brief Summary:
This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia-1 (MCL-1) inhibitor, in participants with selected relapsed/refractory myeloid or B-cell malignancies. The purpose of this study is to evaluate the safety and tolerability of PRT1419 monotherapy and in combination with either azacitidine or venetoclax, describe any dose limiting toxicities (DLTs), define the dosing schedule, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia B-cell Non-Hodgkin Lymphoma Chronic Lymphocytic Leukemia Chronic Myelomonocytic Leukemia Follicular Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma Myelodysplastic Syndromes Myeloproliferative Neoplasm Small Lymphocytic Lymphoma Drug: PRT1419 Drug: Azacitidine Drug: Venetoclax Phase 1

Detailed Description:
This is a multicenter, open-label, dose-escalation, Phase 1 study of PRT1419, a MCL-1 inhibitor, evaluating participants with acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasm (MPN) overlap syndrome, chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and B-cell non-hodgkin lymphoma (NHL) including marginal zone lymphoma, follicular lymphoma or mantle cell lymphoma. Participants in study will receive PRT1419 as monotherapy or in combination with either Azacitidine (AZA) or Venetoclax (VEN). The study includes multiple dose escalations and expansion cohorts for RP2D confirmation.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT1419 Injection as Monotherapy or in Combination With Azacitidine or Venetoclax in Patients With Relapsed/Refractory Myeloid or B-cell Malignancies
Actual Study Start Date : March 22, 2022
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : November 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: PRT1419 Monotherapy
PRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned.
 Drug: PRT1419
PRT1419 will be administered by intravenous infusion
Experimental: PRT1419/Azacitidine Combination
PRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned and Azacitidine will be administered by intravenous or subcutaneous on Days 1 through 7 (or alternatively on Days 1 through 5, 8 and 9) of each 28-day treatment cycle.
 Drug: PRT1419
PRT1419 will be administered by intravenous infusion

Drug: Azacitidine
Azacitidine will be administered by intravenous or subcutaneous
Experimental: PRT1419/Venetoclax Combination
PRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned and Venetoclax will be administered orally after either a 3-day or 5-week ramp-up period to reach 400 mg daily administration, prior to commencing PRT1419 administration.
 Drug: PRT1419
PRT1419 will be administered by intravenous infusion

Drug: Venetoclax
Venetoclax will be administered orally


Outcome Measures
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Primary Outcome Measures :
  1. Dose limiting toxicities (DLT) of PRT1419 [ Time Frame: Baseline through Day 28 ]
    Dose limiting toxicities will be evaluated over the 28-day observation period

  2. Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments [ Time Frame: Baseline through approximately 3 years ]
    Safety and tolerability will be assessed by recording adverse events (AEs), serious adverse events (SAEs), and DLTs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

  3. Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) and schedule of PRT1419 [ Time Frame: Baseline through approximately 2 years ]
    The MTD/RP2D will be established for further investigation in participants with advanced hematologic malignancies


Secondary Outcome Measures :
  1. Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: maximum observed plasma concentration [ Time Frame: Baseline through approximately 3.5 years ]
    PRT1419 pharmacokinetics will be calculated by maximum observed plasma concentration

  2. Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Time to maximal plasma concentration [ Time Frame: Baseline through approximately 3.5 years ]
    PRT1419 pharmacokinetics will be calculated by time to maximal plasma concentration (Tmax)

  3. Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Area under the curve [ Time Frame: Baseline through approximately 3.5 years ]
    PRT1419 pharmacokinetics will be calculated by area under the plasma concentration x time curve (AUC) from h 0 to the last measurable time point (AUC0-last)

  4. Safety and tolerability of PRT1419 in combination with AZA and VEN: AEs, SAEs, CTCAE assessments [ Time Frame: Baseline through approximately 3 years ]
    Safety and tolerability will be assessed by recording adverse events (AEs), serious adverse events (SAEs), and DLTs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

  5. Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall response rate (ORR) [ Time Frame: Baseline through approximately 3.5 years ]
    Anti-tumor activity of PRT1419 based on the measurement of objective response rate (ORR) according to the disease-specific response criteria for malignancies under study

  6. Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Progression-free survival (PFS)/event free survival (EFS) [ Time Frame: Baseline through approximately 3.5 years ]
    Duration from Day 1 to the earliest date of first disease progression, as assessed by the investigator according to the disease-specific response criteria for malignancies under study, or death due to any cause

  7. Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Duration of response (DOR) [ Time Frame: Baseline through approximately 3.5 years ]
    Duration from time of first observed response (CR or PR) to the earliest date of disease progression, as assessed by the investigator according to the disease-specific response criteria for malignancies under study, or death due to any cause

  8. Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall survival (OS) [ Time Frame: Baseline through approximately 3.5 years ]
    Duration from Day 1 until death due to any cause


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:

  • Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures
  • Refractory/relapsed disease, having progressed on prior treatment, and without access to further approved therapies or ineligible for approved therapies, in one of the following disease categories: AML, CMML, MDS, MDS/MPN Overlap Syndrome, CLL/SLL, and B-cell NHLs
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 2
  • Adequate organ function (hematology, hepatic, renal, and coagulation)

Exclusion Criteria:

  • Active inflammatory disorders of the gastrointestinal tract, a history of bariatric surgery or other disorders with the potential for GI malabsorption
  • Cardiac function compromise, as assessed by echocardiogram or protocol-specified biochemical markers of cardiac damage, or protocol-defined clinically significant heart disease
  • History of cerebrovascular accident or transient ischemic attack, within 6 months of screening. Participants with a history of pulmonary embolism must not be symptomatic at enrollment
  • Undergone hematopoietic stem-cell transplantation (HSCT) within the last 90 days or have graft-versus-host disease (GVHD) Grade > 1 at study entry
  • Uncontrolled intercurrent illnesses, poorly controlled hypertension or dyslipidemias, Unstable central nervous system (CNS) metastases
  • Treatment with either OATP1B1, OATP1B3 substrates or strong inhibitors of CYP2C8, CYP3A4, and any medication contraindicated in combination with AZA or VEN
  • Prior exposure to an MCL-1 inhibitor
  • Within 5 half-lives or 14 days (whichever is longer) following the last systemic anti-cancer therapy

  • History of another malignancy except for:

    1. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    2. Adequately treated cervical or breast carcinoma in situ without evidence of disease
    3. Asymptomatic prostate cancer without known metastatic disease and no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for >1 year prior to enrollment
    4. Other malignancy treated with curative intent with no known active disease for > 2 years prior to enrollment
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): NCT05107856


Contacts
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Contact: Study Contact (Please Do Not Disclose Personal Information) See Email PRT1419-03IVstudy@preludetx.com

Locations
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United States, Florida
Mid Florida Hematology and Oncology Center Recruiting
Orange City, Florida, United States, 32763
AdventHealth Bone and Marrow Transplant Center Recruiting
Orlando, Florida, United States, 32804
United States, Maryland
American Oncology Partners of Maryland, PA Recruiting
Bethesda, Maryland, United States, 20817
United States, New Jersey
New Jersey Center for Cancer Research Recruiting
Brick, New Jersey, United States, 08724
United States, New York
Memorial Sloan Kettering Cancer Center - Main Campus Recruiting
New York, New York, United States, 10065
North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists Recruiting
Port Jefferson Station, New York, United States, 11776
United States, Ohio
Gabrail Cancer Center Research Recruiting
Canton, Ohio, United States, 44718
United States, Pennsylvania
Thomas Jefferson University, Sidney Kimmel Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Prelude Therapeutics
More Information
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Responsible Party: Prelude Therapeutics
ClinicalTrials.gov Identifier: NCT05107856    
Other Study ID Numbers: PRT1419-03
First Posted: November 4, 2021    Key Record Dates
Last Update Posted: April 4, 2023
Last Verified: March 2023

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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:
PRT1419
Acute Myeloid Leukemia (AML)
Azacitidine
B-cell Malignancies
B-cell Non-Hodgkin lymphoma
Chronic lymphocytic leukemia (CLL)
Chronic Myelomonocytic Leukemia (CMML)
Follicular Lymphoma
Hematologic Malignancies
 Mantle Cell Lymphoma
Marginal Zone Lymphoma
Myelodysplastic Syndromes (MDS)
Myeloid cell leukemia-1 (MCL-1)
Myeloproliferative Neoplasm (MPN)
Relapsed/Refractory Myeloid
Small lymphocytic lymphoma (SLL)
Venetoclax
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Neoplasms
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, Follicular
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Myelomonocytic, Chronic
Lymphoma, B-Cell
Leukemia, Myelomonocytic, Juvenile
 Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Myelodysplastic-Myeloproliferative Diseases