A Phase 1 Study of JNJ-87189401 (PSMA-CD28 Bispecific Antibody) Combined With JNJ-78278343 (KLK2-CD3 Bispecific Antibody) for Advanced Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 355
- 试验地点
- 20
- 主要终点
- Parts 1, 2C, 3 and 4: Number of Participants With Dose Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of Parts 1, 2A, and 2B of the study is to determine the recommended regimen for Phase 2 (RP2Rs) of combination of JNJ-87189401 with JNJ-78278343 and the purpose of Part 2C of this study is to determine how safe the RP2R(s) of the combination of JNJ-87189401 and JNJ-78278343 is, with or without apalutamide. Part 3 of this study evaluates the safety of the triplet combination of JNJ-87189401 and JNJ-78278343 with standard of care (SOC) lutetium Lu-177 vipivotide tetraxetan. Part 4 of this study further evaluates the safety of the triplet combination of JNJ-87189401 and JNJ-78278343 with JNJ-101556143 in participants with advanced prostate cancer.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the prostate. Adenocarcinoma with small cell or neuroendocrine (NE) features is permitted. However, small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma is disallowed
- •Measurable or evaluable disease per PCWG3 criteria
- •Part 1, Parts 2A, 2B, 3 and 4: Prior orchiectomy or medical castration; participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist), prior to the first dose of study drug and must continue this therapy throughout the treatment phase
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •History of an autoimmune disease within the 12 months prior to signing consent
- •Any of the following within 6 months prior to signature of informed consent: a. myocardial infarction, b. severe or unstable angina, c. clinically significant ventricular arrhythmias, d. congestive heart failure (New York Heart Association [NYHA] class II to IV), e. transient ischemic attack, and f. Cerebrovascular accident
研究组 & 干预措施
Part 1 (Dose Escalation)
Participants will receive JNJ-78278343 + JNJ-87189401 escalated sequentially in Part 1 to select a recommended Phase 2 regimen (RP2R).
干预措施: JNJ-78278343 (Drug)
Part 4
Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) along with JNJ-101556143. Dosing of JNJ-78278343+JNJ-87189401 along with JNJ-101556143 will be escalated sequentially to determine the RP2R of the combinations.
干预措施: JNJ-87189401 (Drug)
Part 3
Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) selected in Part 1 along with standard of care (SOC) treatment with lutetium Lu-177 vipivotide tetraxetan. Dosing of JNJ-78278343+JNJ-87189401 will be escalated sequentially, as per study evaluation team (SET) decision.
干预措施: Lutetium Lu-177 Vipivotide Tetraxetan (Drug)
Part 3
Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) selected in Part 1 along with standard of care (SOC) treatment with lutetium Lu-177 vipivotide tetraxetan. Dosing of JNJ-78278343+JNJ-87189401 will be escalated sequentially, as per study evaluation team (SET) decision.
干预措施: JNJ-78278343 (Drug)
Part 4
Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) along with JNJ-101556143. Dosing of JNJ-78278343+JNJ-87189401 along with JNJ-101556143 will be escalated sequentially to determine the RP2R of the combinations.
干预措施: JNJ-101556143 (Drug)
Part 1 (Dose Escalation)
Participants will receive JNJ-78278343 + JNJ-87189401 escalated sequentially in Part 1 to select a recommended Phase 2 regimen (RP2R).
干预措施: JNJ-87189401 (Drug)
Part 3
Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) selected in Part 1 along with standard of care (SOC) treatment with lutetium Lu-177 vipivotide tetraxetan. Dosing of JNJ-78278343+JNJ-87189401 will be escalated sequentially, as per study evaluation team (SET) decision.
干预措施: JNJ-87189401 (Drug)
Part 4
Participants will receive JNJ-78278343 + JNJ-87189401 at one or more RP2R (s) along with JNJ-101556143. Dosing of JNJ-78278343+JNJ-87189401 along with JNJ-101556143 will be escalated sequentially to determine the RP2R of the combinations.
干预措施: JNJ-78278343 (Drug)
Part 2 (Dose Expansion)
Participants with different disease settings in Parts 2A and 2B will receive JNJ-78278343+JNJ-87189401 at the RP2R selected in Part 1. Participants in Part 2C will receive apalutamide plus continued treatment with JNJ-87189401+JNJ-78278343 doublet.
干预措施: JNJ-78278343 (Drug)
Part 2 (Dose Expansion)
Participants with different disease settings in Parts 2A and 2B will receive JNJ-78278343+JNJ-87189401 at the RP2R selected in Part 1. Participants in Part 2C will receive apalutamide plus continued treatment with JNJ-87189401+JNJ-78278343 doublet.
干预措施: JNJ-87189401 (Drug)
Part 2 (Dose Expansion)
Participants with different disease settings in Parts 2A and 2B will receive JNJ-78278343+JNJ-87189401 at the RP2R selected in Part 1. Participants in Part 2C will receive apalutamide plus continued treatment with JNJ-87189401+JNJ-78278343 doublet.
干预措施: Apalutamide (Drug)
结局指标
主要结局
Parts 1, 2C, 3 and 4: Number of Participants With Dose Limiting Toxicity (DLT)
时间窗: Up to 21 days after first combination dose of study drugs
DLTs are specific adverse events (AEs) and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity.
Number of Participants with Adverse Events (AEs) by Severity
时间窗: Up to 4 years 8 months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 with the exception of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome events, which will be graded by American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Severity scale ranges from grade 1 (mild) to grade 5 (death). 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 (DLT)
时间窗: Up to 21 days after first combination dose of study drugs
DLTs are specific adverse events (AEs) and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity.
次要结局
- Serum Concentrations of JNJ-87189401 and JNJ-78278343(Up to 4 years 8 months)
- Plasma Concentration of JNJ-101556143(Up to 4 years 8 months)
- Number of Participants With Antibodies to JNJ-87189401 and JNJ-78278343(Up to 4 years 8 months)
- Objective Response Rate (ORR)(Up to 4 years 8 months)
- Radiographic Progression-Free Survival (rPFS)(Up to 4 years 8 months)
- Prostate Specific Antigen (PSA) Response Rate(Up to 4 years 8 months)
- Duration of Response (DOR)(Up to 4 years 8 months)
- Part 2: Serum Concentration of JNJ-87189401(Up to 3 years 7 months)
- Number of Participants With Antibodies to JNJ-87189401 and JNJ-78278343(Up to 3 years 7 months)
- Objective Response Rate (ORR)(Up to 3 years 7 months)
- Prostate Specific Antigen (PSA) Response Rate(Up to 3 years 7 months)
- Duration of Response (DOR)(Up to 3 years 7 months)