Adenoid Cystic Carcinoma, Refractory Chronic Myelomonocytic Leukemia, Relapsed/Refractory Acute Myeloid Leukemia, Relapsed/Refractory Advanced Solid Tumors, Relapsed/Refractory Diffuse Large B-cell Lymphoma, Relapsed/Refractory Mantle Cell Lymphoma, Relapsed/Refractory Myelodysplasia, Relapsed/Refractory Myelofibrosis
Conditions
Keywords
PRMT5, PRMT5 Inhibitor
Brief summary
This is a Phase 1 cohort, dose-escalation, dose-expansion study of PRT543 in patients with advanced cancers 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 PRT543.
Detailed description
This is a multicenter, open-label, sequential-cohort, dose-escalation, dose-expansion Phase 1 study of PRT543 in patients with advanced cancers who have exhausted available treatment options. Enrollment will take place concurrently into two distinct patient groups (one for solid tumors/lymphomas and one for hematological malignancies). The study will consist of 2 parts, a dose escalation part, and once the recommended phase 2 dose (RP2D) has been determined, a cohort expansion part involving up to ten separate cohorts. For patients, 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 PRT543.
Interventions
DRUGPRT543
PRT543 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
* Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies * Biomarker-selected solid tumors * Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1 * Adequate organ function (bone marrow, hepatic, renal, cardiovascular) * Female patients 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
* Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases * Requirement of pharmacologic doses of glucocorticoids * Prior treatment with chimeric antigen receptor T cells (CAR-T cells) * HIV positive; known active hepatitis B or C * Known hypersensitivity to any of the components of PRT543 * Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the recommended phase 2 dose (RP2D) and schedule of PRT543 | Baseline through approximately 2 years. | The recommended phase 2 dose (RP2D) and optimal dosing schedule of PRT543 will be established for further investigation in participants with advanced malignancies who have failed prior treatments. |
| To determine the maximally tolerated dose (MTD) | Baseline through approximately 2 years. | The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments. |
| To describe dose limiting toxicities (DLT) of PRT543 | Baseline through Day 28. | Dose limiting toxicities (DLTs) will be evaluated during the first cycle |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543 | Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. | PRT543 pharmacokinetics will be calculated including the time to reach maximum observed plasma concentration |
| To describe the adverse event profile and tolerability of PRT543 | Baseline through approximately 2 years | Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy |
| To determine the maximum observed plasma concentration (Cmax) of PRT543 | Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. | PRT543 pharmacokinetics will be calculated including the maximum observed plasma concentration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| To determine the terminal elimination half-life (t1/2) of PRT543. | Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. | PRT543 pharmacokinetics will be calculated including the terminal elimination half life |
| To determine the area under the plasma concentration versus time curve (AUC) of PRT543 | Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. | PRT543 pharmacokinetics will be calculated including area under the plasma concentration versus time curve. |
Countries
United States
Outcome results
None listed