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Amino Acids

JNJ-64619178

Enzyme Inhibitors

Arginine

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.

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.

JNJ-64619178 capsules to be administered orally.

Janssen Research & Development, LLC Clinical Trial

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).

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.

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

DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.

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.

Number of participants with abnormality in vital signs (temperature, pulse/heart rate, and blood pressure) will be reported.

Number of participants with laboratory abnormalities (serum chemistry, hematology, and coagulation, and disease-related laboratory abnormalities) will be reported.

Number of participants with electrocardiogram(ECG) abnormalities will be reported.

Cmax is the maximum observed plasma concentration.

AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval.

Cmin is the minimum observed plasma concentration.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

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.

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Accumulation Index (RA) is calculated as AUC (0-24) value at steady state divided by AUC (0-24) value after first dose.

Plasma concentration of symmetric dimethyl-arginine (SDMA) will be evaluated.

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.

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.

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%.

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.

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.

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.

Spots Global Cancer Trial Database for lower risk mds