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.

Trial Description

Primary Outcome:

• Number of Participants with Dose-limiting Toxicities (DLTs)

Secondary Outcome:

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