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

Phase 1TerminatedNCT05107856

Prelude Therapeutics21 enrolled

Overview

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).

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia B-cell Non-Hodgkin Lymphoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (9)

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

Outcomes

Primary Outcomes

Dose limiting toxicities (DLT) of PRT1419

Dose limiting toxicities will be evaluated over the 28-day observation period

Time frame: Baseline through Day 28

Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments

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)

Time frame: Baseline through approximately 3 years

Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) and schedule of PRT1419

The MTD/RP2D will be established for further investigation in participants with advanced hematologic malignancies

Time frame: Baseline through approximately 2 years

Secondary Outcomes

Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: maximum observed plasma concentration

PRT1419 pharmacokinetics will be calculated by maximum observed plasma concentration