A Study of PRT811 in Participants With Advanced Solid Tumors, CNS Lymphoma and Gliomas

Advanced Solid Tumor Clinical Trial

Official title:

A Phase 1, Open-Label, Multicenter, Dose Escalation and Expansion Study of PRT811 in Subjects With Advanced Solid Tumors, CNS Lymphoma, and Recurrent High-Grade Gliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04089449
• Other study ID #: PRT811-01
• Status: Completed
• Phase: Phase 1
• Start date: November 6, 2019
• Est. completion date: March 28, 2023

Study information

• Verified date: April 2023
• 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 PRT811, a protein arginine N-methyltransferase (PRMT) 5 inhibitor, in subjects with advanced cancers and high-grade gliomas 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 PRT811.

Description:

This is a multicenter, open-label, dose-escalation, dose-expansion Phase 1 study of PRT811, a PRMT5 inhibitor, in subjects with advanced cancers without any approved or available treatment options including solid tumors, CNS lymphoma, and /or high-grade gliomas. The study will consist of 2 parts, a dose escalation part evaluating subjects with advanced solid tumors, CNS lymphoma, and/or high-grade glioma and a cohort expansion part which will evaluate the safety and efficacy of PRT811 in subjects with advanced solid tumors, and glioblastoma multiforme. For subjects, 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 PRT811.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: March 28, 2023
• Est. primary completion date: March 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Malignancies that are refractory to or intolerant of established therapies known to provide clinical benefit for the malignancy in question, or in the opinion of the Investigator, not be a candidate for such therapies
• Subjects must have recovered from the effects of any prior investigational system therapies
• For subjects with recurrent high-grade glioma or GBM, must have biopsy proven evidence (WHO Grade III or IV) and received external bean fractionated radiotherapy and at least 2 cycles of adjuvant temozolomide chemotherapy. Mutant Glioma must comply with biomarker defined enrollment criterias.
• For biomarker-selected solid tumors: must meet enrollment criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
• Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
• Female subjects 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:

• Untreated concurrent malignancies or malignancies that have been in complete remission for less than one year
• Treatment with strong inhibitors of CYP3A4 for which there are no therapeutic substitutions
• Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
• HIV positive; known active hepatitis B or C
• Known hypersensitivity to any of the components of PRT811

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Glioma
• Recurrent Glioma

Intervention

Drug:
• PRT811
PRT811 will be administered orally

Locations

Country	Name	City	State
United States	Georgia Cancer Center at Augusta University	Augusta	Georgia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	The Ohio State University and Wexner Medical Center	Columbus	Ohio
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Florida Cancer Specialists	Lake Mary	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Yale- New Haven Hospital- Yale Cancer Center	New Haven	Connecticut
United States	Christiana Care Health Services, Christiana Hospital	Newark	Delaware
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Prelude Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To describe dose limiting toxicities (DLT) of PRT811	Dose limiting toxicities will be evaluated through the first cycle	Baseline through Day 21
Primary	To determine the maximally tolerated dose (MTD)	The MTD will be established for further investigation in participants with solid tumors and gliomas	Baseline through approximately 2 years
Primary	To determine the recommended phase 2 dose (RP2D) and schedule of PRT811	The RP2D will be established for further investigation in participants with solid tumors and gliomas	Baseline through approximately 2 years
Secondary	To describe the adverse event profile and tolerability of PRT811	Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy	Baseline through approximately 2 years
Secondary	To describe the pharmacokinetic profile of PRT811	PRT811 pharmacokinetics will be calculated including the maximum observed plasma concentration	Cycle 1 (each cycle is 21 days) on Days 1, 8 and 14. For subsequent cycles, Day 1 of each cycle through the end of study treatment, an average of 6 months
Secondary	To describe any anti-tumor activity of PRT811	Anti-tumor activity of PRT811 will be based on the measurement of objective responses	Baseline through approximately 2 years