A Phase 3 Randomized, Double-blind, Placebo-controlled Study of Pasritamig (JNJ-78278343), a T Cell Engaging Agent Targeting Human Kallikrein 2, With or Without JNJ-87189401, a PSMA-CD28 Costimulatory Agent, Plus Best Supportive Care Versus Best Supportive Care for Late-line Metastatic Castration-resistant Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,203
- 试验地点
- 239
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this study is to evaluate the overall survival (length of time from the start of study to date of death from any cause) for pasritamig (JNJ-78278343) in Part 1 in combination with best supportive care (BSC) and in Part 2 with JNJ-87189401+BSC as compared to placebo with BSC in participants with metastatic castration-resistant prostate cancer (mCRPC; a stage of cancer that has spread beyond the prostate gland and is no longer responding to hormone therapies).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Metastatic castration-resistant prostate cancer (mCRPC): Disease that is metastatic either to bone, any lymph node, or both without clear evidence of other metastatic sites at the time of screening by conventional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) (chest, abdomen, and pelvis) and 99m^Tc bone scan. Visceral disease is not allowed
- •PSA greater than or equal to (≥) 2 nanogram per milliliter (ng/mL) at screening
- •In the opinion of the investigator, the next best treatment option is a clinical trial
- •Participants are required to have had all life-prolonging therapies for which they are clinically eligible in the opinion of the investigator and to which they have access. Prior therapies could have been given in any disease setting (not limited to mCRPC). In particular, prior treatment specifications include receipt of the following:
- •Androgen-receptor pathway inhibitor (ARPI): Must have progressed on at least 1 ARPI and unlikely to benefit from retreatment with another ARPI
- •Taxanes: Required to have received at least 2 previous taxane-based regimens. If a participant has received only 1 taxane regimen, the participant is eligible if:
- •Cabazitaxel is not available
- •The participant's physician deems the participant unsuitable to receive a second taxane regimen due to toxicity risk or prior intolerance Note: a taxane-based regimen consists of at least 2 cycles of a taxane (either as a single agent or in combination with other therapies) administered within the same 2-month period
- •Radioligand therapy: Required to have been previously treated with at least 1 dose of Prostate-specific membrane antigen (PSMA)-targeted lutetium radioligand therapy (eg, lutetium Lu-177 vipivotide tetraxetan), unless one of the following applies:
- •PSMA-targeted lutetium radioligand therapy is unavailable, not accessible, or not clinically indicated.
- •The participant's physician deems the participant unsuitable to receive PSMA-targeted lutetium radioligand therapy.
- •Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi): Required to have been previously treated with PARPi, if the participant has a known germline or somatic BRCA mutation and treatment is available
- •Prior orchiectomy or medical castration (receiving ongoing ADT with a GnRH analog [agonist or antagonist]) prior to the first dose of study treatment and must continue this therapy throughout the treatment phase
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Participants are eligible if they have the following values:
- •A) eGFR ≥ 40 milliliters per minute (mL/min) B) Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) less than or equal to (≤) 3 times the Upper Limit of Normal (ULN) C) Total bilirubin <1.5 times ULN D) Absolute neutrophil count (ANC) ≥ 1.0x10^9/per liter (L) E) Hemoglobin ≥ 8.0 grams per deciliter (g/dL) F) Platelet count ≥ 75x10^9/L
排除标准
- •Venous thromboembolic events within 1 month prior to the first dose of study treatment; uncomplicated (Grade ≤ 2) deep vein thrombosis is not exclusionary
- •Active autoimmune disease within the past 12 months that requires systemic immunosuppressive medications (eg, chronic corticosteroid, methotrexate, or tacrolimus)
- •Participants with Grade 1 or higher fever (≥38ºC) or active infection requiring systemic treatment within 7 days prior to randomization are ineligible. Participants must be afebrile (<38ºC) at the time of study treatment dosing unless approved by medical monitor
- •Clinically significant pulmonary compromise, particularly a requirement for supplemental oxygen use (>2 liters per minute (L/min) by nasal cannula) to maintain adequate oxygenation
- •Prior or concurrent second malignancy (other than the disease under study) for which natural history or treatment could likely interfere with any study endpoints of safety or the efficacy of the study treatment(s)
- •Any of the following within 6 months prior to first dose of study treatment:
- •A) Myocardial infarction B) Severe or unstable angina C) Clinically significant ventricular arrhythmias D) Congestive heart failure (New York Heart Association class II to IV) E) Transient ischemic attack F) Cerebrovascular accident
- •- Prior treatment with any CD3-directed therapy
研究组 & 干预措施
Pasritamig Plus Best Supportive Care (BSC)
Participants will receive the step-up doses of pasritamig intravenously (IV) on Cycle 1 Day 1 (C1D1) and C1D8, and target dose of pasritamig IV on C1D15. From C2D1 onwards participants will receive pasritamig target dose IV every 6 weeks. All Cycles are 6 weeks, except for Cycle 1 which is 8 weeks. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Pasritamig (Biological)
Part 2: Pasritamig+JNJ-87189401+BSC
Participants in Part 2 will receive 2 step-up doses of pasritamig IV followed by the target dose. JNJ-87189401 will be administered with the first target dose of pasritamig. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Best Supportive Care (BSC) (Drug)
Part 1: Pasritamig+Best Supportive Care (BSC)
Participants in Part 1 will receive 2 step-up doses of pasritamig intravenously (IV) followed by the target dose. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Pasritamig (Biological)
Part 1: Pasritamig+Best Supportive Care (BSC)
Participants in Part 1 will receive 2 step-up doses of pasritamig intravenously (IV) followed by the target dose. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Best Supportive Care (BSC) (Drug)
Part 1: Placebo+BSC
Participants in Part 1 will receive 2 step-up doses of placebo IV followed by the target dose. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Placebo (Other)
Part 1: Placebo+BSC
Participants in Part 1 will receive 2 step-up doses of placebo IV followed by the target dose. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Best Supportive Care (BSC) (Drug)
Part 2: Pasritamig+BSC
Participants in Part 2 will receive 2 step-up doses of pasritamig IV followed by the target dose. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Pasritamig (Biological)
Part 2: Pasritamig+BSC
Participants in Part 2 will receive 2 step-up doses of pasritamig IV followed by the target dose. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Best Supportive Care (BSC) (Drug)
Part 2: Pasritamig+JNJ-87189401+BSC
Participants in Part 2 will receive 2 step-up doses of pasritamig IV followed by the target dose. JNJ-87189401 will be administered with the first target dose of pasritamig. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Pasritamig (Biological)
Part 2: Pasritamig+JNJ-87189401+BSC
Participants in Part 2 will receive 2 step-up doses of pasritamig IV followed by the target dose. JNJ-87189401 will be administered with the first target dose of pasritamig. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: JNJ-87189401 (Biological)
Part 2: Placebo +BSC
Participants in Part 2 will receive 2 step-up doses of placebo IV followed by the target dose. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Placebo (Other)
Part 2: Placebo +BSC
Participants in Part 2 will receive 2 step-up doses of placebo IV followed by the target dose. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Best Supportive Care (BSC) (Drug)
Placebo Plus BSC
Participants will receive the step-up doses of placebo IV on C1D1 and C1D8, and target dose of placebo on C1D15. From C2D1 onwards, participants will receive placebo target dose IV every 6 weeks. All Cycles are 6 weeks, except for Cycle 1 which is 8 weeks. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC at the discretion of the physician.
干预措施: Placebo (Other)
Placebo Plus BSC
Participants will receive the step-up doses of placebo IV on C1D1 and C1D8, and target dose of placebo on C1D15. From C2D1 onwards, participants will receive placebo target dose IV every 6 weeks. All Cycles are 6 weeks, except for Cycle 1 which is 8 weeks. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC at the discretion of the physician.
干预措施: Best Supportive Care (BSC) (Drug)
Pasritamig Plus Best Supportive Care (BSC)
Participants will receive the step-up doses of pasritamig intravenously (IV) on Cycle 1 Day 1 (C1D1) and C1D8, and target dose of pasritamig IV on C1D15. From C2D1 onwards participants will receive pasritamig target dose IV every 6 weeks. All Cycles are 6 weeks, except for Cycle 1 which is 8 weeks. Participants will receive study treatment until confirmed progressive disease, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first. All participants may receive BSC (defined as palliative external beam radiation, low dose steroids, pain medication, bone sparing agents, and needed palliative procedures) at the discretion of the physician.
干预措施: Best Supportive Care (BSC) (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to 2 years and 8 months
OS is defined as the time from randomization to date of death due to any cause.
次要结局
- Radiographic Progression-free Survival (rPFS)(Up to 2 years and 8 months)
- Time to Symptomatic Progression(Up to 2 years and 8 months)
- Time to Skeletal-Related Event(Up to 2 years and 8 months)
- Progression-Free Survival (PFS)(Up to 2 years and 8 months)
- Time to Prostate Specific Antigen (PSA) Progression(Up to 2 years and 8 months)
- Number of Participants with Adverse Events (AEs)(Up to 2 years and 8 months)
- Time to Pain Progression (TTPP) as Assessed by the Brief Pain Inventory-Short Form (BPI-SF) Item 3 Worst Pain in 24 Hours(Up to 2 years and 8 months)
- Time to Deterioration in Fatigue as Assessed by the European Organisation For Research And Treatment of Cancer Quality of Life Questionnaire-Core-30 (EORTC QLQ-C30) Fatigue Scale Score(Up to 2 years and 8 months)
- Number of Participants with Abnormalities in Clinical Laboratory Assessments(Up to 2 years and 8 months)