A Study of PRT811 in Participants With Advanced Solid Tumors, CNS Lymphoma and Gliomas
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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, CNS lymphoma, 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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PRT811 PRT811 will be administered orally |
Drug: PRT811
PRT811 will be administered orally
|
Outcome Measures
Primary Outcome Measures
- To describe dose limiting toxicities (DLT) of PRT811 [Baseline through Day 21]
Dose limiting toxicities will be evaluated through the first cycle
- To determine the maximally tolerated dose (MTD) [Baseline through approximately 2 years]
The MTD will be established for further investigation in participants with solid tumors and gliomas
- To determine the recommended phase 2 dose (RP2D) and schedule of PRT811 [Baseline through approximately 2 years]
The RP2D will be established for further investigation in participants with solid tumors and gliomas
Secondary Outcome Measures
- To describe the adverse event profile and tolerability of PRT811 [Baseline through approximately 2 years]
Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
- To describe the pharmacokinetic profile of PRT811 [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]
PRT811 pharmacokinetics will be calculated including the maximum observed plasma concentration
- To describe any anti-tumor activity of PRT811 [Baseline through approximately 2 years]
Anti-tumor activity of PRT811 will be based on the measurement of objective responses
Eligibility Criteria
Criteria
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
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Subjects must have recovered from the effects of any prior investigational system therapies
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For subjects with lymphoma with CNS involvement: must have relapsed or refractory CNS lymphoma, adequate bone marrow reserves and at least one lesion measurable for response using the appropriate response criteria for the type of lymphoma.
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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.
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For biomarker-selected solid tumors: must meet enrollment criteria
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Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
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Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
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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:
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Untreated concurrent malignancies or malignancies that have been in complete remission for less than one year
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Treatment with strong inhibitors of CYP3A4 for which there are no therapeutic substitutions
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Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
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HIV positive; known active hepatitis B or C
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Known hypersensitivity to any of the components of PRT811
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sarah Cannon Research Institute at HealthONE | Denver | Colorado | United States | 80218 |
| 2 | Yale- New Haven Hospital- Yale Cancer Center | New Haven | Connecticut | United States | 06510 |
| 3 | Christiana Care Health Services, Christiana Hospital | Newark | Delaware | United States | 19718 |
| 4 | Florida Cancer Specialists | Lake Mary | Florida | United States | 32746 |
| 5 | Georgia Cancer Center at Augusta University | Augusta | Georgia | United States | 30912 |
| 6 | University of Iowa Hospitals and Clinics | Iowa City | Iowa | United States | 52242 |
| 7 | Washington University School of Medicine - Siteman Cancer Center | Saint Louis | Missouri | United States | 63110 |
| 8 | The Ohio State University and Wexner Medical Center | Columbus | Ohio | United States | 43210 |
| 9 | Thomas Jefferson University, Sidney Kimmel Cancer Center | Philadelphia | Pennsylvania | United States | 19107 |
| 10 | Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Prelude Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRT811-01