A Phase 1b Study of JNJ-78278343, a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2), in Combination With JNJ-95298177, an Antibody Drug Conjugate Targeting Prostate Specific Membrane Antigen, for Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 7
- 主要终点
- Part 1: Number of Participants With Dose-Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to identify the recommended phase 2 combination dose (RP2CD) of JNJ-78278343 in combination with JNJ-95298177 in Part 1 (Dose confirmation) of the study and to determine how safe and tolerable the RP2CD of JNJ-7827834 and JNJ-95298177 with or without JNJ-87189401 is for treatment of participants with metastatic castration-resistant prostate cancer (mCRPC; a stage of prostate cancer where the cancer has spread beyond the prostate and is resistant to hormonal therapy) in Part 2 (Dose expansion) of 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the prostate. Primary small cell carcinoma, carcinoid tumor, neuroendocrine (NE) carcinoma, or large cell NE carcinoma arising in the prostate are not allowed; however, adenocarcinomas with NE features (for example [e.g.], immunohistochemistry [IHC] with both androgen receptor [AR]- and NE-marker positivity) are allowed
- •Must have metastatic castration-resistant prostate cancer (mCRPC)
- •PSA must measure at least 2 nanograms per milliliters (ng/mL) at screening
- •Measurable or evaluable disease
- •Prior orchiectomy or medical castration; or, for 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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Toxicity related to prior anticancer therapy that has not returned to grade less than or equal to (<=) 1 or baseline levels (except for alopecia and vitiligo)
- •Known allergies, hypersensitivity, or intolerance to any of the components (e.g., excipients) of JNJ-78278343, JNJ-95298177, or JNJ-87189401
- •Participants with leptomeningeal disease or brain metastases, with the exception of participants with definitively, locally treated brain metastases that are clinically stable and asymptomatic greater than (>) 2 weeks, and who are off corticosteroid treatment for at least 2 weeks prior to first dose of study treatment
- •Treatment with any anti-cancer or investigational agents within 14 days prior to the first dose of study treatment; specific requirements for certain anti-cancer therapies are as follows:
- •Any T-cell redirecting treatment (e.g., CD3-directed bispecific or Chimeric Antigen Receptor T-cell [CAR-T] therapy) within 90 days prior to the first dose of study treatment
- •Immune checkpoint inhibitors within 6 weeks prior to the first dose of study treatment
- •Radium (Ra) 223 dichloride within 28 days prior to the first dose of study treatment
- •Any prior treatment with kallikrein-related peptidase 2 (KLK2)-targeted therapy
- •Any prior prostate-specific membrane antigen (PSMA)-targeting therapy (that is [i.e.], participants who received PSMA-targeting radioconjugates are excluded) [Parts 2A and 2B only]. Prior PSMA RLT is allowed in Part 1 and required for Part 2C and Part 2D but last dose must be >3 months prior to the first dose of study treatment
- •Any prior antibody drug conjugates (ADCs) with microtubule inhibitor payloads (e.g., auristatins, maytansinoids, tubulysins)
- •Any serious underlying medical conditions or other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments
研究组 & 干预措施
Part 2: Dose Expansion
Participants will receive JNJ-78278343 in combination with JNJ-95298177 at the RP2CD as determined in Part 1 of the study with or without JNJ-87189401 to confirm the safety and anti-tumor activity.
干预措施: JNJ-87189401 (Drug)
Part 2: Dose Expansion
Participants will receive JNJ-78278343 in combination with JNJ-95298177 at the RP2CD as determined in Part 1 of the study with or without JNJ-87189401 to confirm the safety and anti-tumor activity.
干预措施: JNJ-95298177 (Drug)
Part 1: Dose Confirmation
Participants will receive JNJ-78278343 in combination with JNJ-95298177 in a dose de-escalation schedule in accordance with the Bayesian Optimal Interval Design (BOIN) design to determine the recommended phase 2 combination dose (RP2CD) regimen.
干预措施: JNJ-78278343 (Drug)
Part 1: Dose Confirmation
Participants will receive JNJ-78278343 in combination with JNJ-95298177 in a dose de-escalation schedule in accordance with the Bayesian Optimal Interval Design (BOIN) design to determine the recommended phase 2 combination dose (RP2CD) regimen.
干预措施: JNJ-95298177 (Drug)
Part 2: Dose Expansion
Participants will receive JNJ-78278343 in combination with JNJ-95298177 at the RP2CD as determined in Part 1 of the study with or without JNJ-87189401 to confirm the safety and anti-tumor activity.
干预措施: JNJ-78278343 (Drug)
结局指标
主要结局
Part 1: Number of Participants With Dose-Limiting Toxicity (DLT)
时间窗: Up To Day 22
High grade hematologic or non-hematologic toxicities with exceptions and/or toxicities leading to treatment discontinuation will be regarded as DLT.
Number of Participants With Adverse Events (AEs) by Severity
时间窗: Up to 2 years 2 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. 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. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines and ocular events will be graded using the alternative scale provided in the protocol.
次要结局
- Objective Response Rate (ORR)(Up to 2 years 2 months)
- Prostate-Specific Antigen (PSA) Response Rate(Up to 2 years 2 months)
- Time to Response (TTR)(Up to 2 years 2 months)
- Number of Participants With Anti-JNJ-78278343 Antibodies(Up to 2 years 2 months)
- Radiographic Progression-Free Survival (rPFS)(Up to 2 years 2 months)
- Duration of Response (DOR)(Up to 2 years 2 months)
- Serum Concentration of JNJ-78278343(Up to 2 years 2 months)
- Serum Concentration of JNJ-95298177(Up to 2 years 2 months)
- Number of Participants With Anti-JNJ-95298177 Antibodies(Up to 2 years 2 months)
- Serum Concentration of JNJ-87189401(Up to 2 years 2 months)
- Number of Participants With Anti-JNJ-87189401 Antibodies(Up to 2 years 2 months)