Advanced Solid Tumor, Recurrent Glioma
Conditions
Keywords
PRMT5, PRMT5 Inhibitor
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.
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.
Interventions
DRUGPRT811
PRT811 will be administered orally
Sponsors
Prelude Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed