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

Adenoid Cystic Carcinoma Clinical Trial

Official title:

A Phase 1, Open-Label, Multicenter, Dose Escalation, Dose Expansion Study of PRT543 in Patients With Advanced Solid Tumors and Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03886831
• Other study ID #: PRT543-01
• Status: Completed
• Phase: Phase 1
• Start date: February 11, 2019
• Est. completion date: November 16, 2022

Study information

• Verified date: March 2023
• Source: Prelude Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a multicenter, open-label, sequential-cohort, dose-escalation, dose-expansion Phase 1 study of PRT543 in patients with advanced cancers who have exhausted available treatment options. Enrollment will take place concurrently into two distinct patient groups (one for solid tumors/lymphomas and one for hematological malignancies). The study will consist of 2 parts, a dose escalation part, and once the recommended phase 2 dose (RP2D) has been determined, a cohort expansion part involving up to ten separate cohorts. For patients, the study will include a screening phase, a treatment phase, and a post treatment follow-up phase. An end-of-study visit will be conducted within 30 days after the last dose of PRT543.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: November 16, 2022
• Est. primary completion date: November 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• PRT543
PRT543 will be administered orally

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Georgia Cancer Center at Augusta University	Augusta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	The Ohio State University and Wexner Medical Center	Columbus	Ohio
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	MD Anderson Cancer Center	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Florida Cancer Specialists	Lake Mary	Florida
United States	Norton Cancer Institute, St. Matthews Campus	Louisville	Kentucky
United States	Atlantic Health System / Morristown Medical Center	Morristown	New Jersey
United States	PLLC	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health Services, Christiana Hospital	Newark	Delaware
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	UCSF Precision Cancer Medicine Building	San Francisco	California
United States	Florida Cancer Specialist	Sarasota	Florida
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Prelude Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To determine the terminal elimination half-life (t1/2) of PRT543.	PRT543 pharmacokinetics will be calculated including the terminal elimination half life	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.
Other	To determine the area under the plasma concentration versus time curve (AUC) of PRT543	PRT543 pharmacokinetics will be calculated including area under the plasma concentration versus time curve.	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.
Primary	To describe dose limiting toxicities (DLT) of PRT543	Dose limiting toxicities (DLTs) will be evaluated during the first cycle	Baseline through Day 28.
Primary	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.
Primary	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	To describe the adverse event profile and tolerability of PRT543	Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy	Baseline through approximately 2 years
Secondary	To determine the maximum observed plasma concentration (Cmax) of PRT543	PRT543 pharmacokinetics will be calculated including the maximum observed plasma concentration.	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.
Secondary	To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543	PRT543 pharmacokinetics will be calculated including the time to reach maximum observed plasma concentration	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.