A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1, Open-Label, Multicenter, Dose Escalation, Dose Expansion Study of PRT543 in Patients With Advanced Solid Tumors and Hematologic Malignancies

Conditions
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Relapsed/Refractory Advanced Solid Tumors, Relapsed/Refractory Diffuse Large B-cell Lymphoma, Relapsed/Refractory Myelodysplasia, Relapsed/Refractory Myelofibrosis, Adenoid Cystic Carcinoma, Relapsed/Refractory Mantle Cell Lymphoma, Relapsed/Refractory Acute Myeloid Leukemia, Refractory Chronic Myelomonocytic Leukemia

Intervention / Treatment
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* Drug: PRT543


Participation Criteria
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Eligibility Criteria
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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

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: PRT543<br>PRT543 will be administered orally | Drug: PRT543<br>* PRT543 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 PRT543 | Dose limiting toxicities (DLTs) will be evaluated during the first cycle | Baseline through Day 28. | 
| To determine the maximally tolerated dose (MTD) | The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments. | Baseline through approximately 2 years. | 
| To determine the recommended phase 2 dose (RP2D) and schedule of PRT543 | 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. | Baseline through approximately 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe the adverse event profile and tolerability of PRT543 | Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy | Baseline through approximately 2 years | 
| To determine the maximum observed plasma concentration (Cmax) of PRT543 | PRT543 pharmacokinetics will be calculated including the maximum observed plasma concentration. | 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. | 
| To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543 | PRT543 pharmacokinetics will be calculated including the time to reach maximum observed plasma concentration | 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. | 

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