Clinical trial NCT03886831: A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies
Official title: A Phase 1, Open-Label, Multicenter, Dose Escalation, Dose Expansion Study of PRT543 in Patients With Advanced Solid Tumors and Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Prelude Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-03-22
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: To describe dose limiting toxicities (DLT) of PRT543
timeFrame: Baseline through Day 28.
measure: To determine the maximally tolerated dose (MTD)
timeFrame: Baseline through approximately 2 years.
measure: To determine the recommended phase 2 dose (RP2D) and schedule of PRT543
timeFrame: Baseline through approximately 2 years.
Secondary outcomes:
measure: To describe the adverse event profile and tolerability of PRT543
timeFrame: Baseline through approximately 2 years
measure: To determine the maximum observed plasma concentration (Cmax) of PRT543
timeFrame: 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.
measure: To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543
timeFrame: 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:
measure: To determine the terminal elimination half-life (t1/2) of PRT543.
timeFrame: 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.
measure: To determine the area under the plasma concentration versus time curve (AUC) of PRT543
timeFrame: 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.
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: San Francisco
country: United States
facility: UCSF Precision Cancer Medicine Building
state: California
city: Newark
country: United States
facility: Christiana Care Health Services, Christiana Hospital
state: Delaware
city: Lake Mary
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Morristown
country: United States
facility: Atlantic Health System / Morristown Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University and Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: PLLC
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
References: