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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 18
- 主要终点
- Part 1 and Part 2: Number of Participants with Dose-limiting Toxicities (DLTs)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: JNJ-64619178 (Drug)
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.
干预措施: JNJ-64619178 (Drug)
结局指标
主要结局
Part 1 and Part 2: Number of Participants with Dose-limiting Toxicities (DLTs)
时间窗: Approximately 3 years
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.
次要结局
- Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of JNJ-64619178(Approximately 3 years)
- Part 1 and Part 2: Apparent Total Systemic Clearance of Drug (CL/F) after Extravascular Administration(Approximately 3 years)
- Part 1 and Part 2: Accumulation Index (RA)(Approximately 3 years)
- Part 1 and Part 2: Number of Participants with Adverse Events (AE)(Approximately 3 years)
- Part 1 and Part 2: Number of Participants with Abnormal Vital Signs(Approximately 3 years)
- Part 1 and Part 2: Number of Participants with Laboratory Abnormalities(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)(Approximately 3 years)
- Part 1 and Part 2: Minimum Plasma Concentration (Cmin)(Approximately 3 years)
- Part 1 and Part 2: Volume of Distribution at Steady-State Influenced by the Fraction Absorbed (Vss/F)(Approximately 3 years)
- Part 1 and Part 2: Plasma Decay Half-Life (t1/2)(Approximately 3 years)
- Part 1 and Part 2: Plasma Concentration of Symmetric Dimethyl-Arginine (SDMA)(Approximately 3 years)
- Part 1: Percentage of Participants with B cell non-Hodgkin lymphoma (NHL) Showing Overall Response of Partial Response (PR) or Better(Approximately 3 years)
- Part 1 and Part 2: Number of Participants with AE by Severity(Approximately 3 years)
- Part 1 and Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities(Approximately 3 years)
- Part 1: Duration of Response(Approximately 3 years)
- Part 2: Overall Improvement Rate(Approximately 3 years)
- Part 1: Percentage of Participants with Solid Tumors Showing Overall Response of PR or Better(Approximately 3 years)
- Part 2: Red Blood Cell (RBC) Transfusion Independence (TI) Rate(Approximately 3 years)
- Part 1: Clinical Benefit Rate(Approximately 3 years)