A Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64619178, an Inhibitor of Protein Arginine Methyltransferase 5 (PRMT5) in Participants With Advanced Cancers

Official Title

A Phase 1, First-in-Human, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64619178, an Inhibitor of Protein Arginine Methyltransferase 5 (PRMT5) in Subjects With Advanced Cancers

Summary:

The purpose of the study is to identify the maximum tolerated dose (MTD) of JNJ-64619178 in participants with relapsed/refractory B cell non-Hodgkin lymphoma (NHL) or advanced solid tumours and also to identify the recommended Phase 2 dose(s) (RP2Ds) of JNJ-64619178 for NHL and advanced solid tumours (Part 1) and to confirm the tolerability of JNJ-64619178 in participants with lower risk myelodysplastic syndromes (MDS) (Part 2).

Trial Description

Primary Outcome:

• Part 1 and Part 2: Number of Participants with Dose-limiting Toxicities (DLTs)

Secondary Outcome:

• Part 1 and Part 2: Number of Participants with Adverse Events (AE)
• Part 1 and Part 2: Number of Participants with AE by Severity
• Part 1 and Part 2: Number of Participants with Abnormal Vital Signs
• Part 1 and Part 2: Number of Participants with Laboratory Abnormalities
• Part 1 and Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities
• Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of JNJ-64619178
• Part 1 and Part 2: Area Under the Plasma Concentration Versus Time Curve From Time Zero to End of Dosing Interval (AUCtau)
• Part 1 and Part 2: Minimum Plasma Concentration (Cmin)
• Part 1 and Part 2: Plasma Decay Half-Life (t1/2)
• Part 1 and Part 2: Volume of Distribution at Steady-State Influenced by the Fraction Absorbed (Vss/F)
• Part 1 and Part 2: Apparent Total Systemic Clearance of Drug (CL/F) after Extravascular Administration
• Part 1 and Part 2: Accumulation Index (RA)
• Part 1 and Part 2: Plasma Concentration of Symmetric Dimethyl-Arginine (SDMA)
• Part 1: Percentage of Participants with B cell non-Hodgkin lymphoma (NHL) Showing Overall Response of Partial Response (PR) or Better
• Part 1: Percentage of Participants with Solid Tumours Showing Overall Response of PR or Better
• Part 1: Duration of Response
• Part 1: Clinical Benefit Rate
• Part 2: Red Blood Cell (RBC) Transfusion Independence (TI) Rate
• Part 2: Overall Improvement Rate

The study is designed to determine the maximum tolerated dose (MTD) of JNJ-64619178, and to select a dose(s) and regimen(s) that may be used in future clinical development. Study evaluations will include safety, pharmacokinetics, biomarkers and efficacy evaluations (Disease Assessments). Adverse events will be evaluated throughout the study. The study is divided into 4 periods: a screening phase, a pharmacokinetic run-in phase, a treatment phase, and a post treatment follow-up phase. An end-of-treatment visit will be completed less than or equal (<=) 30 days (+7 days) after the last dose of study drug or prior to the start of a new anticancer therapy, whichever comes first.

View this trial on ClinicalTrials.gov