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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05107856
• Other study ID #: PRT1419-03
• Status: Terminated
• Phase: Phase 1
• Start date: March 22, 2022
• Est. completion date: January 19, 2024

Study information

• Verified date: January 2024
• Source: Prelude Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: January 19, 2024
• Est. primary completion date: January 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• B-cell Non-Hodgkin Lymphoma
• Chronic Lymphocytic Leukemia
• Chronic Myelomonocytic Leukemia
• Follicular Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms
• Preleukemia
• Small Lymphocytic Lymphoma

Intervention

Drug:
• PRT1419
PRT1419 will be administered by intravenous infusion
• Azacitidine
Azacitidine will be administered by intravenous or subcutaneous
• Venetoclax
Venetoclax will be administered orally

Locations

Country	Name	City	State
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	New Jersey Center for Cancer Research	Brick	New Jersey
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center - Main Campus	New York	New York
United States	Mid Florida Hematology and Oncology Center	Orange City	Florida
United States	AdventHealth Bone and Marrow Transplant Center	Orlando	Florida
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists	Port Jefferson Station	New York

Sponsors (1)

Lead Sponsor	Collaborator
Prelude Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities (DLT) of PRT1419	Dose limiting toxicities will be evaluated over the 28-day observation period	Baseline through Day 28
Primary	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)	Baseline through approximately 3 years
Primary	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	Baseline through approximately 2 years
Secondary	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	Baseline through approximately 3.5 years
Secondary	Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Time to maximal plasma concentration	PRT1419 pharmacokinetics will be calculated by time to maximal plasma concentration (Tmax)	Baseline through approximately 3.5 years
Secondary	Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Area under the curve	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)	Baseline through approximately 3.5 years
Secondary	Safety and tolerability of PRT1419 in combination with AZA and VEN: 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)	Baseline through approximately 3 years
Secondary	Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall response rate (ORR)	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	Baseline through approximately 3.5 years
Secondary	Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Progression-free survival (PFS)/event free survival (EFS)	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	Baseline through approximately 3.5 years
Secondary	Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Duration of response (DOR)	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	Baseline through approximately 3.5 years
Secondary	Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall survival (OS)	Duration from Day 1 until death due to any cause	Baseline through approximately 3.5 years