A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS

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

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 tumors and also to identify the recommended Phase 2 dose(s) (RP2Ds) of JNJ-64619178 for NHL and advanced solid tumors (Part 1) and to confirm the tolerability of JNJ-64619178 in participants with lower risk myelodysplastic syndromes (MDS) (Part 2).

Study Overview

• Status: Completed
• Conditions: Neoplasms; Myelodysplastic Syndromes; Non-Hodgkin Lymphoma; Solid Tumor, Adult
• Intervention / Treatment: Drug: JNJ-64619178

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6E 1M7
      • St. Paul's Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G1Z5
      • Princess Margaret Cancer Centre University Health Network
• Germany
  • Düsseldorf, Germany, 40225
    • Universitaetsklinikum Duesseldorf
  • Frankfurt am Main, Germany, 60590
    • Goethe Universität Frankfurt
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig
• Israel
  • Haifa, Israel, 34362
    • Carmel Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky MC
• Spain
  • Badalona, Spain, 08916
    • Hosp. Univ. Germans Trias I Pujol
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28040
    • Hosp Univ Fund Jimenez Diaz
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Salamanca, Spain, 37007
    • Hosp Clinico Univ de Salamanca
  • Seville, Spain, 41013
    • Hosp. Virgen Del Rocio
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Specialist and Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• B cell non-Hodgkin lymphoma (NHL) or solid tumors, or lower risk MDS
• At least 1 measurable site of disease for B cell-NHL and solid tumors
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Adequate organ function
• Women of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and prior to the first dose of study drug. Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 90 days after receiving the last dose of study drug

Exclusion Criteria:

• History of, or known, central nervous system (CNS) involvement
• Prior solid organ transplantation
• Either of the following: a) Received an autologous stem cell transplant less than or equal (<=) 9 months before the first dose of study drug B) Prior treatment with allogenic stem cell transplant
• History of malignancy (other than the disease under study) within 3 years before the first administration of study drug. Exceptions include squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
• Known allergies, hypersensitivity, or intolerance to JNJ-64619178 or its excipient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose escalation and RP2D Selection; Participants with solid tumors or non-Hodgkin lymphoma (NHL) will receive JNJ-64619178 orally as per the assigned sequential cohorts and doses will be escalated based on the review of all available data including, but not limited to, pharmacokinetic, pharmacodynamic, safety, and clinical activity. One or more recommended Phase 2 dose(s) (RP2Ds) may be determined for further exploration.	Drug: JNJ-64619178; JNJ-64619178 capsules to be administered orally.
Experimental: Part 2:Dose Confirmation and Expansion; Participants with myelodysplastic syndromes (MDS) will receive JNJ-64619178 at a dose less than or equal to the RP2D selected in Part 1 for 24 weeks, or longer if there is evidence of clinical benefit. The dose level of JNJ-64619178 may be adjusted based on observed toxicities.	Drug: JNJ-64619178; JNJ-64619178 capsules to be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: Number of Participants with Dose-limiting Toxicities (DLTs)	DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.	Approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: Number of Participants with Adverse Events (AE)	AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.	Approximately 3 years
Part 1 and Part 2: Number of Participants with AE by Severity	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 4 (Life-threatening). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.	Approximately 3 years
Part 1 and Part 2: Number of Participants with Abnormal Vital Signs	Number of participants with abnormality in vital signs (temperature, pulse/heart rate, and blood pressure) will be reported.	Approximately 3 years
Part 1 and Part 2: Number of Participants with Laboratory Abnormalities	Number of participants with laboratory abnormalities (serum chemistry, hematology, and coagulation, and disease-related laboratory abnormalities) will be reported.	Approximately 3 years
Part 1 and Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities	Number of participants with electrocardiogram(ECG) abnormalities will be reported.	Approximately 3 years
Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of JNJ-64619178	Cmax is the maximum observed plasma concentration.	Approximately 3 years
Part 1 and Part 2: Area Under the Plasma Concentration Versus Time Curve From Time Zero to End of Dosing Interval (AUCtau)	AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval.	Approximately 3 years
Part 1 and Part 2: Minimum Plasma Concentration (Cmin)	Cmin is the minimum observed plasma concentration.	Approximately 3 years
Part 1 and Part 2: Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Approximately 3 years
Part 1 and Part 2: Volume of Distribution at Steady-State Influenced by the Fraction Absorbed (Vss/F)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady state which is estimated by (D/AUC[0-infinity])* (AUMC[0-infinity])/(AUC[0-infinity]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time. All these parameters will be assessed as influenced by the fraction absorbed.	Approximately 3 years
Part 1 and Part 2: Apparent Total Systemic Clearance of Drug (CL/F) after Extravascular Administration	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	Approximately 3 years
Part 1 and Part 2: Accumulation Index (RA)	Accumulation Index (RA) is calculated as AUC (0-24) value at steady state divided by AUC (0-24) value after first dose.	Approximately 3 years
Part 1 and Part 2: Plasma Concentration of Symmetric Dimethyl-Arginine (SDMA)	Plasma concentration of symmetric dimethyl-arginine (SDMA) will be evaluated.	Approximately 3 years
Part 1: Percentage of Participants with B cell non-Hodgkin lymphoma (NHL) Showing Overall Response of Partial Response (PR) or Better	Overall response rate (ORR) is defined as the percentage of participants who have a PR or better. Per Lugano classification, PR is defined as greater than or equal (>=) 50 percent (%) decrease in size of target lesions.	Approximately 3 years
Part 1: Percentage of Participants with Solid Tumors Showing Overall Response of PR or Better	Overall response rate (ORR) is defined as the percentage of participants who have a PR or better. PR criteria in solid tumors (RECIST) is >= 30 percent (%) decrease in the sum of the diameters of all index lesions compared with baseline in 2 observations at least 4 weeks apart, in absence of new lesions or unequivocal progression of non-index lesions.	Approximately 3 years
Part 1: Duration of Response	Duration of response (DOR) will be calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease (PD), as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first. PD (per RECIST 1.1) defined as at least 20% increase in the sum of the longest diameters of index lesions or unequivocal progression of non-index lesions. Per Lugano classification, PD: target lesions larger; clear progression of non-target lesions; or new tumor lesions; new or recurrent bone marrow involvement; splenomegaly + 2 centimeter (cm) or +50%.	Approximately 3 years
Part 1: Clinical Benefit Rate	Clinical benefit rate is defined as percentage of participants who have a complete response (CR), PR and sustained stable disease of 12 weeks or more. Sustained stable disease of 12 weeks or more is defined as participants with stable disease assessment maintained for about 12 weeks or longer from baseline. Per Lugano classification CR is defined as no detectable disease by computed tomography (CT) or positron emission tomography (PET)/CT scan. Evaluation criteria as per RECIST 1.1 for CR is defined as disappearance of all lesions in 2 consecutive observations not less than 4 weeks apart.	Approximately 3 years
Part 2: Red Blood Cell (RBC) Transfusion Independence (TI) Rate	Percentage of participants with TI, defined as being without any transfusion during any consecutive 8 weeks (56 days) between the first dose of study drug and treatment discontinuation.	Approximately 3 years
Part 2: Overall Improvement Rate	Overall improvement rate is defined as the percentage of participants achieving complete remission (bone marrow: less than or equal to (<=)5% myeloblasts with normal maturation of all cell lines; Peripheral blood: hemoglobin >=11 gram per deciliter (g/dL); platelets >=100*109/liter(L); neutrophils >=1.0*109/L; blasts, 0%), partial remission (All complete remission criteria if abnormal before treatment except: Bone marrow blasts decreased by >=50% over pretreatment but still >5% Cellularity and morphology not relevant), or hematologic improvement (HI) (Erythroid response [pretreatment, <11 g/dL]; Platelet response (pretreatment, <100*10^9/L); Neutrophil response (pretreatment, <1*10^9/L); Progression or relapse after HI) according to modified International Working Group (IWG) criteria.	Approximately 3 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2018
• Primary Completion (Actual): September 25, 2025
• Study Completion (Actual): September 25, 2025

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: June 20, 2018
• First Posted (Actual): June 29, 2018

Study Record Updates

• Last Update Posted (Estimated): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Intermediate-1 risk MDS; Low risk MDS; Low-risk MDS; Lower risk MDS; Lower-risk MDS; Intermediate 1 risk MDS
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Neoplasms; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; JNJ-64619178
• Other Study ID Numbers: CR108485; 64619178EDI1001 (Other Identifier: Janssen Research & Development, LLC); 2018-000067-87 (EudraCT Number); 2024-515254-24-00 (Registry Identifier: EUCT number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No