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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Advanced Solid Tumor, Recurrent Glioma

Intervention / Treatment
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* Drug: PRT811


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRT811<br>PRT811 will be administered orally | Drug: PRT811<br>* PRT811 will be administered orally<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PRMT5, PRMT5 Inhibitor