A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies

NCT03886831 | Completed Phase 1 FDA Drug

• 1 other identifier: PRT543-01
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 23

Brief Summary

This is a Phase 1 cohort, dose-escalation, dose-expansion study of PRT543 in patients with advanced cancers who have exhausted available treatment options. The purpose of this study is to define a safe dose and schedule to be used in subsequent development of PRT543.

Conditions

Relapsed/Refractory Advanced Solid Tumors; Relapsed/Refractory Diffuse Large B-cell Lymphoma; Relapsed/Refractory Myelodysplasia; Relapsed/Refractory Myelofibrosis; Adenoid Cystic Carcinoma; Relapsed/Refractory Mantle Cell Lymphoma; Relapsed/Refractory Acute Myeloid Leukemia; Refractory Chronic Myelomonocytic Leukemia

Keywords

PRMT5; PRMT5 Inhibitor

Outcome Measures

Primary Outcomes (3)

• To describe dose limiting toxicities (DLT) of PRT543

  Dose limiting toxicities (DLTs) will be evaluated during the first cycle

  Baseline through Day 28.

• To determine the maximally tolerated dose (MTD)

  The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments.

  Baseline through approximately 2 years.

• To determine the recommended phase 2 dose (RP2D) and schedule of PRT543

  The recommended phase 2 dose (RP2D) and optimal dosing schedule of PRT543 will be established for further investigation in participants with advanced malignancies who have failed prior treatments.

  Baseline through approximately 2 years.

Secondary Outcomes (3)

• To describe the adverse event profile and tolerability of PRT543

  Baseline through approximately 2 years

• To determine the maximum observed plasma concentration (Cmax) of PRT543

  Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.

• To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543

  Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.

Other Outcomes (2)

• To determine the terminal elimination half-life (t1/2) of PRT543.

  Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.

• To determine the area under the plasma concentration versus time curve (AUC) of PRT543

  Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.

Study Arms (1)

PRT543

EXPERIMENTAL

PRT543 will be administered orally

Drug: PRT543

Interventions

PRT543 DRUG

PRT543 will be administered orally

PRT543

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
• Biomarker-selected solid tumors
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
• Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
• Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial

You may not qualify if:

• Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases
• Requirement of pharmacologic doses of glucocorticoids
• Prior treatment with chimeric antigen receptor T cells (CAR-T cells)
• HIV positive; known active hepatitis B or C
• Known hypersensitivity to any of the components of PRT543
• Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation

Sponsors & Collaborators

• Prelude Therapeutics: lead

Study Sites (23)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

UCSF Precision Cancer Medicine Building

San Francisco, California, 94158, United States

Location

Christiana Care Health Services, Christiana Hospital

Newark, Delaware, 19718, United States

Location

Florida Cancer Specialists

Lake Mary, Florida, 32746, United States

Location

Florida Cancer Specialist

Sarasota, Florida, 34232, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, 40207, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Atlantic Health System / Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

The Ohio State University and Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

PLLC

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, Large B-Cell, Diffuse; Anemia, Refractory, with Excess of Blasts; Primary Myelofibrosis; Carcinoma, Adenoid Cystic; Lymphoma, Mantle-Cell; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Anemia, Refractory; Anemia; Hematologic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Myeloproliferative Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Leukemia, Myeloid; Leukemia; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: March 22, 2019
• Study Start: February 11, 2019
• Primary Completion: November 16, 2022
• Study Completion: November 16, 2022
• Last Updated: March 28, 2023

Record last verified: 2023-03

Locations

US (23)