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

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 1

Conditions: Solid Tumor, Adult; Neoplasms; Myelodysplastic Syndromes; Non-Hodgkin Lymphoma

Treatments: Drug: JNJ-64619178

Study type: Interventional

Funder types: Industry

Identifiers

NCT03573310

2018-000067-87 (EudraCT Number)

CR108485

64619178EDI1001 (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 114 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

114 participants in 2 patient groups

Part 1: Dose escalation and RP2D Selection

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64619178

Part 2:Dose Confirmation and Expansion

Experimental group

Description:

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.

Treatment:

Drug: JNJ-64619178