A Phase 1, First-in-Human, Dose Escalation Study of JNJ-90189892 for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 155
- 试验地点
- 16
- 主要终点
- Number of Participants with Adverse events (AEs) by Severity
研究概览
简要总结
The purpose of Part 1 (Dose Escalation) of the study is to assess the effective dose (recommended Phase 2 dose[s] [RP2Ds]) that can be safely administered, and dosing regimens of JNJ-90189892 in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) or R/R higher-risk type of myelodysplastic neoplasms (MDS [type of cancer of the blood and bone marrow, which does not respond to treatment or comes back after treatment]). The purpose of Part 2 (Cohort Expansion) is to further assess the safety, tolerability and efficacy in participants with R/R AML or higher-risk types of MDS at the RP2D regimen(s). The purpose of Part 3 and 4 is to assess the effective dose (recommended Phase 2 combination dose [RP2CD]) that can be safely administered, and dosing regimens of JNJ-90189892 in combination with azacitadine (AZA) + venetoclax (VEN) in participants with R/R AML (part 3) and newly diagnosed (ND) AML (part 4).
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. For Parts 1, 2, and 3: Have a diagnosis, per the world health organization (WHO) 2022 criteria, of (a) Parts 1, 2, and 3: Acute myeloid leukemia (AML) or (b) Parts 1 and 2: Moderate high, high, or very high-risk myelodysplastic neoplasms (MDS) per Molecular International Prognostic Scoring System (IPSS-M); B. For Part 4 only: Previously untreated acute myeloid leukemia (AML) per the WHO 2022 criteria
- •Body weight that is greater than or equals to (>=) 40 kg
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Have adequate renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Estimated Glomerular Filtration Rate (eGFR) >=40 milligrams per minute (mL/min) computed with the calculator on the national kidney foundation website
- •Participants must have laboratory parameters in the required range
排除标准
- •Has a medical history of clinically significant pulmonary compromise, particularly the current need for supplemental oxygen use to maintain adequate oxygenation
- •Has evidence of uncontrolled systemic viral, bacterial, or fungal infection. Antimicrobial prophylaxis is permitted
- •All participants- Has known allergies, hypersensitivity, or intolerance to JNJ-90189892 or its excipients; Parts 3 and 4- Has known allergies, hypersensitivity, or intolerance to venetoclax (VEN), azacitadine (AZA), or their excipients
- •Had major surgery or had significant traumatic injury within 14 days of planned first dose of JNJ-90189892
- •Had a prior or concurrent second malignancy with natural history or treatment likely to interfere with any study endpoints of safety or the efficacy of the study treatment
- •Has known active central nervous system involvement
研究组 & 干预措施
JNJ-90189892: In Combination with Azacitadine (AZA)+ Venetoclax (VEN)
Participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) in Part 3 will receive JNJ-90189892+ AZA+VEN to determine the recommended Phase 2 combination dose (RP2CD). The starting JNJ-90189892 dose regimen in Part 3 will be at least 1 dose level below the highest dose level cleared in Part 1 as determined by the SET. In Part 4 participants with newly diagnosed (ND) AML will receive JNJ-90189892+ AZA+VEN starting from the JNJ-90189892 dose level determined safe in Part 3 by the SET.
干预措施: Azacitadine (AZA) (Drug)
JNJ-90189892: In Combination with Azacitadine (AZA)+ Venetoclax (VEN)
Participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) in Part 3 will receive JNJ-90189892+ AZA+VEN to determine the recommended Phase 2 combination dose (RP2CD). The starting JNJ-90189892 dose regimen in Part 3 will be at least 1 dose level below the highest dose level cleared in Part 1 as determined by the SET. In Part 4 participants with newly diagnosed (ND) AML will receive JNJ-90189892+ AZA+VEN starting from the JNJ-90189892 dose level determined safe in Part 3 by the SET.
干预措施: Venetoclax (VEN) (Drug)
JNJ-90189892: Monotherapy
Participants will receive JNJ-90189892 in Part 1 (Dose escalation) of the study and the dose levels will be escalated sequentially based on the decisions of the study evaluation team (SET) until the recommended phase 2 dose (RP2D) has been identified. Participants in Part 2 (Dose expansion) will receive JNJ-90189892 at the RP2D determined in Part 1.
干预措施: JNJ-90189892 (Drug)
JNJ-90189892: In Combination with Azacitadine (AZA)+ Venetoclax (VEN)
Participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) in Part 3 will receive JNJ-90189892+ AZA+VEN to determine the recommended Phase 2 combination dose (RP2CD). The starting JNJ-90189892 dose regimen in Part 3 will be at least 1 dose level below the highest dose level cleared in Part 1 as determined by the SET. In Part 4 participants with newly diagnosed (ND) AML will receive JNJ-90189892+ AZA+VEN starting from the JNJ-90189892 dose level determined safe in Part 3 by the SET.
干预措施: JNJ-90189892 (Drug)
结局指标
主要结局
Number of Participants with Adverse events (AEs) by Severity
时间窗: From screening untill 30 days after last dose of study drug (that is approximately 2.5 years)
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Part 1: Number of Participants with Dose-Limiting Toxicity (DLTs)
时间窗: At least 14 days
DLT is defined as any toxicity that requires discontinuation of treatment, any Grade 5 toxicity; Non-hematologic toxicity (Grade 3 or 4) and Hematologic toxicity.
次要结局
- Serum Concentration of JNJ-90189892(Up to approximately 2.5 years)
- Area Under the Curve Over a Dosing Interval (AUC tau) of JNJ-90189892(Up to approximately 2.5 years)
- Maximum Observed Plasma Concentration (Cmax) of JNJ-90189892(Up to approximately 2.5 years)
- Minimum Observed Plasma Concentration (Cmin) of JNJ-90189892(Up to approximately 2.5 years)
- Number of Participants with Presence of Anti-JNJ-90189892 Antibodies(Up to approximately 2.5 years)
- Complete Response (CR) in Acute Myeloid Leukemia (AML)(Up to approximately 2.5 years)
- Overall Response (OR) in Myelodysplastic Neoplasms (MDS)(Up to approximately 2.5 years)
- Complete Response in MDS(Up to approximately 2.5 years)
- Duration of Response (DOR)(Up to approximately 2.5 years)
- Time to Response (TTR)(Up to approximately 2.5 years)
- Number of Participants Achieving Transfusion Independence(Up to approximately 2.5 years)
- Part 4 Only: Overall Survival (OS)(Up to approximately 2.5 years)
- Part 4 Only: Event-Free Survival (EFS)(Up to approximately 2.5 years)