A Phase 1 Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 144
- 试验地点
- 11
- 主要终点
- Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
研究概览
简要总结
The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D[s]) of JNJ-69086420 in Part 1 (Dose Escalation), to determine safety and preliminary signs of clinical activity at the RP2D(s) in Part 2 (Dose Expansion), to determine safety of JNJ-69086420 at the RP2D(s) as a combination therapy in Part 3 (combination therapy) and to determine safety of JNJ-69086420 at the RP2D(s) in participants with metastatic hormone-sensitive prostate cancer (mHSPC) in 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
- Male
- 接受健康志愿者
- 否
入选标准
- •For Part 1, Part 2, Part 3: Metastatic castration resistant prostate cancer (mCRPC) with histologic confirmation of adenocarcinoma (adenocarcinoma with small-cell or neuroendocrine features is allowed) with prior exposure to at least one androgen receptor (AR) targeted therapy (for example [e.g.], abiraterone acetate, enzalutamide, apalutamide, darolutamide). In addition: Part 1: prior taxane or other chemotherapy is acceptable but not required. Part 2a: prior taxane or other chemotherapy required, Part 2b: no prior taxane or other chemotherapy, Part 2c: mCRPC that has progressed after prior treatment with lutetium Lu-177 vipivotide tetraxetan, with or without prior chemotherapy, Part 3: prior taxane or other chemotherapy is acceptable but not required & For Part 4a: metastatic HSPC, For Part 4b: disease that can be treated with less than or equal to (<=) 5 radiation fields and no visceral metastases
- •Parts 1, 2 & 3: 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. This criterion does not apply to Part 4
- •Palliative radiotherapy (e.g. soft tissue lesions) must be completed greater than (>) 2 weeks prior to start of study drug except for palliative radiotherapy for pain (e.g., bone pain), which may be used any time prior to first dose
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ functions as reflected in laboratory parameters
排除标准
- •Prior treatment with radium Xofigo (Ra 223 dichloride), strontium, samarium, or other radioconjugate therapy, other systemic anti-neoplastic therapy <=30 days prior to the first dose of study drug except for luteinizing hormone-releasing hormone agonists/antagonists or GnRH agonists/antagonists. Novel androgen axis drugs <=14 days prior to the first dose of study drug. In addition: Part 2b: Must not have received prior treatment with chemotherapy (eg, docetaxel) or poly ADP ribose polymerase (PARP) inhibitors, Part 2c: Prior treatment with lutetium Lu-177 vipivotide tetraxetan is required, but must have been completed >42 days prior to first dose of study drug, Part 3: Must not have received prior treatment with JNJ-78278343, Part 4: Must not have received ADT or AR-targeted therapy less than or equal to (<=) 56 days prior to first dose of study drug
- •Known history of myelodysplastic syndrome, leukemia, or hematological malignancy with features suggestive of myelodysplastic syndrome/acute myeloid leukemia at any timepoint
- •Toxicity from prior anticancer therapy has not resolved to baseline levels or to Grade <= 1 (except alopecia, radiation tissue fibrosis, or peripheral neuropathy)
- •Known allergies, hypersensitivity, or intolerance to JNJ-69086420 or its excipients and protein therapeutics. For Part 3, known allergies, hypersensitivity, or intolerance to JNJ-78278343 or its excipients or protein therapeutics
- •Active or chronic hepatitis B or hepatitis C infection
研究组 & 干预措施
Part 3: Combination Therapy
Participants will receive JNJ-69086420 at the determined RP2D(s) and fixed dose of JNJ-78278343.
干预措施: JNJ-69086420 (Drug)
Part 4: HSPC Expansion
Participants with HSPC will receive JNJ-69086420 at the RP2D(s) in Part 4(a), and JNJ-69086420 following stereotactic body radiation therapy in Part 4(b).
干预措施: Stereotactic body radiation therapy (Radiation)
Part 4: HSPC Expansion
Participants with HSPC will receive JNJ-69086420 at the RP2D(s) in Part 4(a), and JNJ-69086420 following stereotactic body radiation therapy in Part 4(b).
干预措施: JNJ-69086420 (Drug)
Part 3: Combination Therapy
Participants will receive JNJ-69086420 at the determined RP2D(s) and fixed dose of JNJ-78278343.
干预措施: JNJ-78278343 (Drug)
Part 1: Dose Escalation
Participants will receive JNJ-69086420 with one or multiple doses. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
干预措施: JNJ-69086420 (Drug)
Part 2: Dose Expansion
Participants in one or more cohorts will receive JNJ-69086420 at the RP2D(s) determined in Part 1.
干预措施: JNJ-69086420 (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
时间窗: Up to 2 years and 4 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.
Part 1: Number of Participants with Dose-Limiting Toxicity (DLT)
时间窗: Up to 2 years and 4 months
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Number of Participants with AEs by Severity
时间窗: Up to 2 years and 4 months
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.
次要结局
- Area Under the Serum Concentration-time Curve From Time Zero to t Time (AUC[0-t]) of JNJ-69086420(Up to 2 years and 4 months)
- Overall Response Rate (ORR)(Up to 2 years and 4 months)
- Number of Participants With Anti-JNJ-69086420 Antibodies(Up to 2 years and 4 months)
- Part 3: Serum Concentration of JNJ-78278343(Up to 2 years and 4 months)
- Percentage of Participants with Prostate Specific Antigen (PSA) Response(Up to 2 years and 4 months)
- Maximum Observed Serum Concentration/Radioactivity (Cmax) of JNJ-69086420(Up to 2 years and 4 months)
- Time to Reach Maximum Observed Serum Concentration/Radioactivity (Tmax) of JNJ-69086420(Up to 2 years and 4 months)
- Part 3:Number of Participants With Anti-JNJ-78278343 Antibodies(Up to 2 years and 4 months)