A Phase 2 Trial of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 351
- 试验地点
- 59
- 主要终点
- Objective Response Rate (ORR) Cohort D
研究概览
简要总结
The purpose of this study is to evaluate the effectiveness, safety and tolerability of nivolumab followed by ipilimumab, in subjects with metastatic castration resistant prostate cancer (mCRPC).
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
- 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
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Current evidence of metastatic disease documented by either bone lesions on radionuclide bone scan and/or soft tissue lesions on computerized tomography/magnetic resonance imaging (CT/MRI).
- •Ongoing androgen deprivation therapy (ADT) with a Gonadotropin-releasing hormone (GnRH) analogue or a surgical/medical castration with testosterone level of ≤1.73nmol/L (50ng/dL)
- •For crossover phase for participants originally randomized to Arm D3 or Arm D4 only:
- •Previously randomized to Arm D3 or D4; had histologic confirmation of adenocarcinoma of the prostate and evidence of Stage IV disease (as defined by American Joint Committee of Cancer criteria (AJCC criteria) prior to randomization
排除标准
- •Presence of visceral metastases in the liver
- •Active brain metastases or leptomeningeal metastases
- •Active, known, or suspected autoimmune disease or infection
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •For crossover phase for participants originally randomized to Arm D3 or Arm D4 only:
- •Prior radiation therapy within 14 days prior to first dose of nivolumab combined with ipilimumab
- •Have received systemic anti-cancer therapy after the last dose of study treatment (ipilimumab or cabazitaxel)
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Cohort A (Arm A)
干预措施: Nivolumab (Biological)
Cohort A (Arm A)
干预措施: Ipilimumab (Biological)
Cohort B (Arm B)
干预措施: Nivolumab (Biological)
Cohort B (Arm B)
干预措施: Ipilimumab (Biological)
Cohort C (Arm C)
干预措施: Nivolumab (Biological)
Cohort C (Arm C)
干预措施: Ipilimumab (Biological)
Cohort D (Arm D1)
干预措施: Nivolumab (Biological)
Cohort D (Arm D1)
干预措施: Ipilimumab (Biological)
Cohort D (Arm D2)
干预措施: Nivolumab (Biological)
Cohort D (Arm D2)
干预措施: Ipilimumab (Biological)
Cohort D (Arm D3)
干预措施: Ipilimumab (Biological)
Cohort D (Arm D4)
干预措施: Cabazitaxel (Drug)
Cohort D (Arm D4)
干预措施: Prednisone (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Cohort D
时间窗: From randomization to the date of objectively documented progression or the date of subsequent systemic anti-cancer therapy, whichever occurred first (assessed up to approximately 61 months)
In Cohort D, ORR is defined as the percentage of participants who had confirmed complete or partial BOR by BICR among randomized subjects with measurable disease at baseline as entered in Interactive Response Technologies web-based system (IWRS). For participants without documented progression or subsequent therapy, all available response assessments will contribute to the BOR assessment. Partial Response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor assessments were performed every 8 weeks (± 7 days) for 6 months since treatment initiation and thereafter every 12 weeks (± 7 days). Confidence-interval based on Clopper Pearson method.
Radiographic Progression-Free Survival (rPFS) for Cohort D
时间窗: From randomization and the first date of documented progression or death due to any cause, whichever occurs first (assessed up to approximately 61 months)
Radiographic progression-free survival (rPFS) is defined as the time between the date of randomization and the first date of documented progression per BICR or death due to any cause, whichever occurs first. The following progressive diseases were collected, documented and assessed as below: Radiographic progression per BICR assessment 1. Bone disease progression by (Prostate Cancer Working Group) PCWG2 2. Non-bone soft tissue disease progression by RECIST v1.1 Progressive disease is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (the appearance of one or more new lesions is also considered progression). Based on Kaplan-Meier estimates.
Objective Response Rate (ORR) Cohorts B and C Per BICR
时间窗: From first dose to the date of objectively documented progression or the date of subsequent systemic anti-cancer therapy, whichever occurred first (assessed up to approximately 61 months)
Objective response rate (ORR) is defined as the percent of participants who had confirmed complete or partial best overall response (BOR) per retrospective Blinded Independent Central Review (BICR) among treated participants with measurable disease at baseline. For participants without documented progression by RECIST v1.1 or subsequent therapy, all available response assessments contributed to the BOR assessment. Partial Response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor assessments were performed every 8 weeks (± 7 days) for 6 months since treatment initiation and thereafter every 12 weeks (± 7 days). Confidence-interval based on Clopper Pearson method.
Radiographic Progression Free Survival (rPFS) for Cohorts B and C Per BICR
时间窗: From first dose to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months)
Radiographic progression-free survival (rPFS) is defined as the time between the date of first treatment and the first date of documented radiographic progression or death due to any cause, whichever occurs first. The following progressive diseases were collected, documented and assessed as below: Radiographic progression per retrospective Blinded Independent Central Review (BICR) assessment 1. Bone disease progression by Prostate Cancer Working Group (PCWG2) 2. Non-bone soft tissue disease progression by RECIST v1.1 Progressive disease is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (the appearance of one or more new lesions is also considered progression). Based on Kaplan-Meier estimates.
次要结局
- Radiographic/Clinical Progression Free Survival (rcPFS) for Cohorts B and C(From first dose to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months))
- Radiographic/Clinical Progression Free Survival (rcPFS) for Cohort D(From randomization and the first date of documented progression or death due to any cause, whichever occurs first (assessed up to approximately 93 months))
- Overall Survival (OS) Cohorts B and C(From first dose to the date of death due to any cause (assessed up to approximately 61 months))
- Overall Survival (OS) Cohort D(From randomization to the date of death due to any cause (assessed up to approximately 93 months))
- Prostate-Specific Antigen Response Rate (PSA-RR) Cohorts B and C(From baseline to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months))
- Prostate-Specific Antigen Response Rate (PSA-RR) Cohort D(From baseline to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 93 months))
- The Number of Participants Experiencing Adverse Events (AEs) in Cohorts A, B and C(From first dose to 30 days after last dose of study therapy (an average of 2.8 months assessed up to approximately 18.2 months))
- The Number of Participants Experiencing Adverse Events (AEs) in Cohort D(From first dose to 30 days after last dose of study therapy (an average of 6.19 months assessed up to approximately 26.8 months))
- The Number of Participants Experiencing Serious Adverse Events (SAEs) in Cohorts A, B and C(From first dose to 30 days after last dose of study therapy (an average of 2.8 months assessed up to approximately 18.2 months))
- The Number of Participants Experiencing Serious Adverse Events (SAEs) in Cohort D(From first dose to 30 days after last dose of study therapy (an average of 6.19 months assessed up to approximately 26.8 months))
- The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation in Cohorts A, B and C(From first dose to 30 days after last dose of study therapy (an average of 2.8 months assessed up to approximately 18.2 months))
- The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation in Cohort D(From first dose to 30 days after last dose of study therapy (an average of 6.19 months assessed up to approximately 26.8 months))
- The Number of Participants Experiencing Immune Mediated Adverse Events in Cohorts A, B and C(From first dose to 100 days after last dose of study therapy (an average of 2.8 months assessed up to approximately 20.7 months))
- The Number of Participants Experiencing Immune Mediated Adverse Events in Cohort D(From first dose to 100 days after last dose of study therapy (an average of 8.48 months assessed up to approximately 29.09 months))
- The Number of Participants Who Died in Cohorts A, B and C(From first dose to 100 days after last dose of study therapy (an average of 2.8 months assessed up to approximately 20.7 months).)
- The Number of Participants Who Died in Cohort D(From first dose to 100 days after last dose of study therapy (an average of 8.48 months assessed up to approximately 29.09 months))
- The Number of Participants With Changes in Laboratory Values From Baseline in Cohorts A, B and C(From first dose to 30 days after last dose of study therapy (an average of 2.8 months assessed up to approximately 18.2 months))
- The Number of Participants With Liver Function Laboratory Abnormalities in Cohort D(From first dose to 30 days after last dose of study therapy (an average of 6.19 months assessed up to approximately 26.8 months))
- The Number of Participants With Changes in Laboratory Values From Baseline in Cohort D(From first dose to 30 days after last dose of study therapy (an average of 6.19 months assessed up to approximately 26.8 months))
- The Number of Participants With Liver Function Laboratory Abnormalities in Cohorts A, B and C(From first dose to 30 days after last dose of study therapy (an average of 2.8 months assessed up to approximately 18.2 months))
- The Number of Participants With Thyroid Function Laboratory Abnormalities in Cohort A, B and C(From first dose to 30 days after last dose of study therapy (an average of 2.8 months assessed up to approximately 18.2 months))
- The Number of Participants With Thyroid Function Laboratory Abnormalities in Cohort D(From first dose to 30 days after last dose of study therapy (an average of 6.19 months assessed up to approximately 26.8 months))
- Changes in Pain Severity as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Scores Cohorts B and C(At baseline and Week 4 (Cycle 2))
- Changes in Pain Severity as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Scores Cohort D(At baseline and 4 weeks after first dose.)
- Change in Cancer-Related Symptoms and Quality of Life (QoL) by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire Cohort D(At baseline and 4 weeks after first dose.)
- Change From Baseline in Health Status and Health Utility by 3-level EuroQol Five Dimensions (EQ-5D-3L) Questionnaire Cohorts B and C(At baseline and at Week 4 of Cycle 2.)
- Change From Baseline in Health Status and Health Utility by 3-level EuroQol Five Dimensions (EQ-5D-3L) Questionnaire Cohort D(At baseline and 4 weeks after first dose.)