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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor; Recurrent Glioma
• Intervention / Treatment: Drug: PRT811

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 615-329-7274; Email: CANN.REFMAL655@SarahCannon.com

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale- New Haven Hospital- Yale Cancer Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health Services, Christiana Hospital
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Florida Cancer Specialists
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Siteman Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University and Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Sidney Kimmel Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRT811; PRT811 will be administered orally	Drug: PRT811; PRT811 will be administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe dose limiting toxicities (DLT) of PRT811	Dose limiting toxicities will be evaluated through the first cycle	Baseline through Day 21
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Prelude Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2019
• Primary Completion (Actual): March 28, 2023
• Study Completion (Actual): March 28, 2023

Study Registration Dates

• First Submitted: September 11, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: PRMT5; PRMT5 Inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: PRT811-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No