A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Subjects With Relapsed or Refractory AML
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 主要终点
- Part 1: Type of dose-limiting toxicity (DLT)
研究概览
简要总结
The purpose of this study is to characterize the safety and tolerability of JNJ-63709178 and identify the recommended Phase 2 dose(s) (RP2D) and schedule for JNJ-63709178 in Part 1 and to characterize the safety and tolerability of JNJ-63709178 at the RP2D(s) in Part 2.
详细描述
This is first-in-human (FIH) Phase 1, open-label (identity of assigned study drug will be known), multicenter, dose escalation study with dose expansion to identify the RP2D and to evaluate the safety, tolerability, and preliminary antitumor activity of JNJ-63709178 in adult participants with relapsed or refractory acute myeloid leukemia (AML) who are ineligible for or have exhausted standard therapeutic options. The study will be conducted in 2 parts: dose escalation and dose expansion. The study is divided into 3 periods: a Screening Phase (within 28 days before the first dose of study drug), a Treatment Phase (first dose of study drug until the last dose of study drug) and a Post-treatment Follow-up Phase (up to the end of study participation or end of study). Participants' safety will be monitored throughout the study.
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
- •A diagnosis of acute myeloid leukemia (AML) according to the World Health Organization 2008 criteria with relapsed or refractory disease and ineligible for or have exhausted standard therapeutic options
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Hematology laboratory parameters within the Protocol specified range
- •Chemistry laboratory parameters within the Protocol specified range
- •A woman of childbearing potential must have a negative highly sensitive serum (beta human chorionic gonadotropin [b-hCG]) or urine test prior to the first dose of study drug
排除标准
- •Acute promyelocytic leukemia
- •Active central nervous system involvement
- •Prior solid organ transplantation
- •Prior hematopoietic stem cell transplant within 6 months of enrollment. If the participant had an allogenic transplant there must be no apparent signs of graft versus host disease and participants must have discontinued all immunosuppressive therapies for at least 4 weeks
- •Prior treatment with a CD123xCD3 bispecific agent, T cells expressing CD123 specific chimeric antigen receptor, or toxin-conjugated to CD123 antibodies; prior treatment with naked anti-CD123 monoclonal antibody is permitted
研究组 & 干预措施
Part 1: Dose Escalation
Participants will receive JNJ-63709178 in Part 1 (in different cohorts). Each subsequent cohort will receive JNJ-63709178 at an increased dose level. Ascending doses may be given initially to minimize or prevent cytokine release syndrome. Dose escalation will continue until the maximum tolerated dose is reached or all planned doses are administered.
干预措施: JNJ-63709178 (Drug)
Part 2: Dose Expansion
Participants will receive JNJ-63709178 at the recommended Phase 2 dose(s) (RP2D) determined in dose expansion phase.
干预措施: JNJ-63709178 (Drug)
结局指标
主要结局
Part 1: Type of dose-limiting toxicity (DLT)
时间窗: Up to Day 28
Part 2: Number of participants with adverse events and serious adverse events
时间窗: Up to 1.5 years
Part 1: Number of participants with dose-limiting toxicity (DLT)
时间窗: Up to Day 28
Part 2: Number of participants with adverse events by severity
时间窗: Up to 1.5 years
次要结局
- Part 2: Serum concentration of JNJ-63709178(Up to 1.5 years)
- Part 2: Systemic cytokine concentration(Up to 1.5 years)
- Part 2: JNJ-63709178 Receptor occupancy(Up to 1.5 years)
- Part 2: Anti- JNJ-63709178 antibodies concentration(Up to 1.5 years)
- Part 2: Event-free survival (EFS)(Up to 1.5 years)
- Part 2: Relapse-free survival (RFS)(Up to 1.5 years)
- Part 2: Number of participants with depletion of CD123 expressing cells(Up to 1.5 years)
- Part 2: Concentration of markers of T cell activation(Up to 1.5 years)
- Part 2: Overall response rate (ORR)(Up to 1.5 years)