A Study of PRT1419 Injection in Patients With Relapsed/Refractory Hematologic Malignancies

Sponsor

Prelude Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05107856

Collaborator

(none)

Enrollment

Locations

Arm

23.3

Anticipated Duration (Months)

4.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia 1 (MCL1) inhibitor, in patients with relapsed/refractory hematologic malignancies. The purpose of this study is to define the dosing schedule, maximally tolerated dose and/or estimate the optimal biological dose to be used in subsequent development of PRT1419.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Myeloproliferative Neoplasm	Drug: PRT1419	Phase 1

Detailed Description

This is a multicenter, open-label, dose-escalation Phase 1 study of PRT1419, a MCL1 inhibitor, evaluating patients as part of a 28-day treatment cycle in adult patients with acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), high-risk myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) overlap syndrome. The study will employ a "3+3" dose escalation design. The dose may be escalated until a minimum safe and biologically effective dose or MTD is reached.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 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 Study of PRT1419 Injection in Patients With Relapsed/Refractory Hematologic Malignancies

Actual Study Start Date :

Mar 22, 2022

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PRT1419 PRT1419 will be administered by intravenous infusion	Drug: PRT1419 PRT1419 will be administered by intravenous infusion

Arm

Intervention/Treatment

Experimental: PRT1419

PRT1419 will be administered by intravenous infusion

Drug: PRT1419

PRT1419 will be administered by intravenous infusion

Outcome Measures

Primary Outcome Measures

Dose limiting toxicities (DLT) of PRT1419 [Baseline through Day 28]
Dose limiting toxicities will be evaluated through the first cycle
Minimum safe and biologically-effective dose [Baseline through approximately 1.5 years]
The minimum safe and biologically-effective dose will be established for further investigation in participants with advanced hematologic malignancies
Recommended phase 2 dose (RP2D) and schedule of PRT1419 [Baseline through approximately 1.5 years]
The RP2D will be established for further investigation in participants with advanced hematologic malignancies

Secondary Outcome Measures

Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments [Baseline through approximately 2 years]
Safety and tolerability will be assessed by recording adverse events (AEs) and serious adverse events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE)
Pharmacokinetic profile of PRT1419: maximum observed plasma concentration [Baseline through approximately 2 years]
PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration
Anti-tumor activity of PRT1419: measurement of objective responses [Baseline through approximately 2 years]
Anti-tumor activity of PRT1419 based on the measurement of objective responses to PRT1419 according to the disease-specific response criteria for patients with hematologic malignancies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 2
Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
Left ventricular ejection fraction of ≥ 50%
All patients must have recovered from the effects of any prior cancer related therapy, radiotherapy, or surgery (toxicity no greater than Grade 1).
All patients on prior investigational agents must wait at least 5 half-lives of the agent in question, or 14 days, whichever is longer before enrollment into the trial, and until any toxicities of the prior investigational agent have resolved to Grade 1 or a baseline state
Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use a highly effective method of contraception during the trial
AML patients only: Pathologically confirmed diagnosis of AML as defined by the WHO Classification and patients with targeted mutations must have been treated with appropriate therapy for their disease

White blood cell count < 25 × 10^9/L. Hydroxyurea or leukapheresis are permitted to meet this criterion

CMML patients only: intermediate-2 or high risk per CMML-specific prognostic scoring system (CPSS) or clinical/molecular CPSS (CPSS-mol) criteria. Must have failed at least 4-6 cycles of prior therapy with a hypomethylating agent
High Risk MDS - MDS/MPN Overlap Syndrome: intermediate, high, or very high risk by International Prognostic Scoring System-Revised [IPSS-R] criteria that is relapsed or refractory to approved therapies, including at least 4-6 cycles of a hypomethylating agent, or MDS/MPN Overlap Syndrome (displaying both fibrosis and dysplastic features)

Exclusion Criteria:

Known hypersensitivity to any of the components of PRT1419
Female patients who are pregnant or lactating
Active inflammatory disorders of the gastrointestinal tract, or patients with GI malabsorption
Mean QTcF interval of > 480 msec
History of heart failure, additional risk factors for arrhythmias or requiring concomitant medications that prolong the QT/QTc interval
Elevated cardiac troponin or evidence of recent cardiac injury
HIV positive; known active hepatitis B or C
Hematopoietic stem-cell transplantation within the last 90 days or have GVHD Grade > 1 at study entry
Uncontrolled intercurrent illnesses
Treatment with either OATP1B1, OATP1B3 substrates or strong inhibitors of CYP2C8
Prior exposure to an MCL1 inhibitor
History of another malignancy except for:

Malignancy treated with curative intent with no known active disease for > 2 years prior to study start
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without evidence of disease
Other concurrent low-grade malignancies (i.e., chronic lymphocytic leukemia (CLL) (Rai 0)) may be considered after consultation with Sponsor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mid Florida Hematology and Oncology Center	Orange City	Florida	United States	32763
2	AdventHealth Bone and Marrow Transplant Center	Orlando	Florida	United States	32804
3	New Jersey Center for Cancer Research	Brick	New Jersey	United States	08724
4	North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists	Port Jefferson Station	New York	United States	11776
5	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
6	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania	United States	19107
7	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030