PRT1419 as Monotherapy or in Combination With Azacitidine or Venetoclax in R/R Myeloid or B-cell Malignancies

NCT ID: NCT05107856

Last Updated: 2024-01-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-22
• Study Completion Date: 2024-01-19

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).

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PRT1419 Monotherapy

PRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned.

Group Type: EXPERIMENTAL

PRT1419

Intervention Type: DRUG

PRT1419 will be administered by intravenous infusion

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.

Group Type: EXPERIMENTAL

PRT1419

Intervention Type: DRUG

PRT1419 will be administered by intravenous infusion

Azacitidine

Intervention Type: DRUG

Azacitidine will be administered by intravenous or subcutaneous

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.

Group Type: EXPERIMENTAL

PRT1419

Intervention Type: DRUG

PRT1419 will be administered by intravenous infusion

Venetoclax

Intervention Type: DRUG

Venetoclax will be administered orally

Interventions

PRT1419

PRT1419 will be administered by intravenous infusion

Intervention Type: DRUG

Azacitidine

Azacitidine will be administered by intravenous or subcutaneous

Intervention Type: DRUG

Venetoclax

Venetoclax will be administered orally

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prelude Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mid Florida Hematology and Oncology Center

Orange City, Florida, United States

AdventHealth Bone and Marrow Transplant Center

Orlando, Florida, United States

American Oncology Partners of Maryland, PA

Bethesda, Maryland, United States

New Jersey Center for Cancer Research

Brick, New Jersey, United States

Memorial Sloan Kettering Cancer Center - Main Campus

New York, New York, United States

North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists

Port Jefferson Station, New York, United States

Gabrail Cancer Center Research

Canton, Ohio, United States

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

PRT1419-03

Identifier Type: -

Identifier Source: org_study_id