A Study of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer (CheckMate 650) (CheckMate 650)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02985957 |
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Recruitment Status :
Active, not recruiting
First Posted : December 7, 2016
Results First Posted : April 24, 2023
Last Update Posted : April 24, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Prostate Cancer | Biological: Nivolumab Biological: Ipilimumab Drug: Cabazitaxel Drug: Prednisone | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 351 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2 Trial of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer |
| Actual Study Start Date : | March 26, 2017 |
| Actual Primary Completion Date : | April 5, 2022 |
| Estimated Study Completion Date : | October 6, 2026 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: Cohort A (Arm A) |
Biological: Nivolumab
Specified dose on specified days
Other Names:
Biological: Ipilimumab Specified dose on specified days
Other Names:
|
| Experimental: Cohort B (Arm B) |
Biological: Nivolumab
Specified dose on specified days
Other Names:
Biological: Ipilimumab Specified dose on specified days
Other Names:
|
| Experimental: Cohort C (Arm C) |
Biological: Nivolumab
Specified dose on specified days
Other Names:
Biological: Ipilimumab Specified dose on specified days
Other Names:
|
| Experimental: Cohort D (Arm D1) |
Biological: Nivolumab
Specified dose on specified days
Other Names:
Biological: Ipilimumab Specified dose on specified days
Other Names:
|
| Experimental: Cohort D (Arm D2) |
Biological: Nivolumab
Specified dose on specified days
Other Names:
Biological: Ipilimumab Specified dose on specified days
Other Names:
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| Experimental: Cohort D (Arm D3) |
Biological: Ipilimumab
Specified dose on specified days
Other Names:
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| Experimental: Cohort D (Arm D4) |
Drug: Cabazitaxel
Specified dose on specified days Drug: Prednisone Specified dose on specified days |
- Objective Response Rate (ORR) Cohorts B and C [ Time Frame: 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 Investigator 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.
- Objective Response Rate (ORR) Cohort D [ Time Frame: 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 Cohorts B and C [ Time Frame: 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 Investigator assessment
- Bone disease progression by Prostate Cancer Working Group (PCWG2)
- 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.
- Radiographic Progression-Free Survival (rPFS) for Cohort D [ Time Frame: 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
- Bone disease progression by (Prostate Cancer Working Group) PCWG2
- 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.
- Radiographic/Clinical Progression Free Survival (rcPFS) for Cohorts B and C [ Time Frame: 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) is the time between first dose and first documented progression or death due to any cause, whichever occurred first.
Radiographic progression per Investigator assessment:
- Bone disease progression by Prostate Cancer Working Group (PCWG2)
- Non-bone soft tissue disease progression by RECIST v1.1
Clinical progression per investigator assessment:
- Need for palliative radiation therapy involving more than one site, OR
- Surgery of kyphoplasty to any neoplastic lesion, OR
- Cancer-associated clinical deterioration determined by treating physician. Progressive disease is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum 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.
- Radiographic/Clinical Progression Free Survival (rcPFS) for Cohort D [ Time Frame: 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/clinical progression-free survival (rcPFS) is the time between first dose and first documented progression or death due to any cause, whichever occurred first.
Radiographic progression per Investigator assessment:
- Bone disease progression by Prostate Cancer Working Group (PCWG2)
- Non-bone soft tissue disease progression by RECIST v1.1
Clinical progression per investigator assessment:
- Need for palliative radiation therapy involving more than one site, OR
- Surgery of kyphoplasty to any neoplastic lesion, OR
- Cancer-associated clinical deterioration determined by treating physician. Progressive disease is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum 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.
- Overall Survival (OS) Cohorts B and C [ Time Frame: From first dose to the date of death due to any cause (assessed up to approximately 61 months) ]
Overall survival (OS) is defined as the time from first treatment to the date of death from any cause. For participants who were alive, their survival time was censored at the last known alive date. Overall survival was censored for participants at the date of first treatment if they had no follow-up.
Based on Kaplan-Meier estimates.
- Overall Survival (OS) Cohort D [ Time Frame: From randomization to the date of death due to any cause (assessed up to approximately 61 months) ]
Overall survival (OS) is defined as the time from randomization to the date of death from any cause. For participants who were alive, their survival time was censored at the last known alive date. Overall survival was censored for participants at the date of first treatment if they had no follow-up.
Based on Kaplan-Meier estimates.
- Prostate-Specific Antigen Response Rate (PSA-RR) Cohorts B and C [ Time Frame: From baseline to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months) ]
The percent of participants with a 50% or greater decrease in prostate-specific antigen (PSA) from baseline to the lowest post-baseline PSA result. BBaseline evaluations or events are defined as evaluations or events that occur before the date and time of the first dose of study treatment. Evaluations on the same date and time of the first dose of study treatment were considered as baseline evaluations.
Confidence-interval based on Clopper Pearson method.
- Prostate-Specific Antigen Response Rate (PSA-RR) Cohort D [ Time Frame: From baseline to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months) ]
The percent of participants with a 50% or greater decrease in prostate-specific antigen (PSA) from baseline to the lowest post-baseline PSA result. Baseline evaluations or events are defined as evaluations or events that occur before the date and time of the first dose of study treatment. Evaluations on the same date and time of the first dose of study treatment were considered as baseline evaluations.
Confidence-interval based on Clopper Pearson method.
- The Number of Participants Experiencing Adverse Events (AEs) in Cohorts A, B and C [ Time Frame: 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) ]An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation in a participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
- The Number of Participants Experiencing Adverse Events (AEs) in Cohort D [ Time Frame: From first dose to 30 days after last dose of study therapy (an average of 4.83 months assessed up to approximately 26.5 months) ]An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation in a participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
- The Number of Participants Experiencing Serious Adverse Events (SAEs) in Cohorts A, B and C [ Time Frame: 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) ]A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
- The Number of Participants Experiencing Serious Adverse Events (SAEs) in Cohort D [ Time Frame: From first dose to 30 days after last dose of study therapy (an average of 4.83 months assessed up to approximately 26.5 months) ]A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
- The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation in Cohorts A, B and C [ Time Frame: 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) ]An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
- The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation in Cohort D [ Time Frame: From first dose to 30 days after last dose of study therapy (an average of 4.83 months assessed up to approximately 26.5 months) ]An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
- The Number of Participants Experiencing Immune Mediated Adverse Events in Cohorts A, B and C [ Time Frame: 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) ]Immune-mediated adverse events (IMAEs) are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.
- The Number of Participants Experiencing Immune Mediated Adverse Events in Cohort D [ Time Frame: From first dose to 100 days after last dose of study therapy (an average of 4.83 months assessed up to approximately 29.5 months). ]Immune-mediated adverse events (IMAEs) are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.
- The Number of Participants Who Died in Cohorts A, B and C [ Time Frame: 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). ]Death due to any cause.
- The Number of Participants Who Died in Cohort D [ Time Frame: From first dose to 100 days after last dose of study therapy (an average of 4.83 months assessed up to approximately 29.5 months). ]Death due to any cause.
- The Number of Participants With Changes in Laboratory Values From Baseline in Cohorts A, B and C [ Time Frame: 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 a change in laboratory values from baseline Grade in Cohorts A, B and C.
- The Number of Participants With Changes in Laboratory Values From Baseline in Cohort D [ Time Frame: From first dose to 30 days after last dose of study therapy (an average of 4.83 months assessed up to approximately 26.5 months) ]The number of participants with an change in laboratory values from baseline Grade in Cohort D.
- The Number of Participants With Liver Function Laboratory Abnormalities in Cohorts A, B and C [ Time Frame: 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 laboratory abnormalities in specific liver tests based on SI conventional units.
ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal
- The Number of Participants With Liver Function Laboratory Abnormalities in Cohort D [ Time Frame: From first dose to 30 days after last dose of study therapy (an average of 4.83 months assessed up to approximately 26.5 months) ]
The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units.
ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal
- The Number of Participants With Thyroid Function Laboratory Abnormalities in Cohort A, B and C [ Time Frame: 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 laboratory abnormalities in specific thyroid tests based on SI conventional units.
TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
- The Number of Participants With Thyroid Function Laboratory Abnormalities in Cohort D [ Time Frame: From first dose to 30 days after last dose of study therapy (an average of 4.83 months assessed up to approximately 26.5 months) ]
The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units.
TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
- Changes in Pain Severity as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Scores Cohorts B and C [ Time Frame: At baseline and Week 4 (Cycle 2) ]Change between Mean BPI-SF scores at baseline and week 4 (cycle 2). The BPI-SF measures pain severity through the use of a numerical rating scale. Participants rate the severity of their pain at its ''worst,'' ''least,'' and ''average'' in the last 24 hours using an 11-point numerical rating scale with anchors of ''0 = no pain'' and ''10 = pain as bad as you can imagine.'' A higher score = a "worse" outcome. Pain Severity Score = Mean of items 3-6 (pain at its worst, pain at its least). Baseline evaluations or events are defined as evaluations or events that occur before the date and time of the first dose of study treatment. Evaluations on the same date and time of the first dose of study treatment were considered as baseline evaluations.
- Changes in Pain Severity as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Scores Cohort D [ Time Frame: At baseline and 4 weeks after first dose. ]Change between Mean BPI-SF scores at baseline and week 4 (cycle 2). The BPI-SF measures pain severity through the use of a numerical rating scale. Participants rate the severity of their pain at its ''worst,'' ''least,'' and ''average'' in the last 24 hours using an 11-point numerical rating scale with anchors of ''0 = no pain'' and ''10 = pain as bad as you can imagine.'' A higher score = a "worse" outcome. Pain Severity Score = Mean of items 3-6 (pain at its worst, pain at its least). Baseline evaluations or events are defined as evaluations or events that occur before the date and time of the first dose of study treatment. Evaluations on the same date and time of the first dose of study treatment were considered as baseline evaluations.
- Change in Cancer-Related Symptoms and Quality of Life (QoL) by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire Cohort D [ Time Frame: At baseline and 4 weeks after first dose. ]The Functional Assessment of Cancer Therapy - Prostate (FACT-P) is a multidimensional, self-report Quality of Life (QoL) instrument designed for use with prostate cancer patients. It consists of 27 core items. The Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, which assesses patient function in 4 domains: Physical, Social/Family, Emotional, and Functional well-being. This is further supplemented by the Prostate Cancer Subscale (PCS), 12 disease-specific items to assess for prostate-related symptoms. Each item is rated from 0 (Not at all) to 4 (Very much) and combined to produce subscale scores for each domain, a Trial Outcome Index which is based on the Physical and Functional well-being scales and the PCS as well as a total score which ranges from 0 to 156. Higher scores represent better QoL. Baseline evaluations or events were defined as those that occur before or on the date and time of the first dose of study treatment.
- Change From Baseline in Health Status and Health Utility by 3-level EuroQol Five Dimensions (EQ-5D-3L) Questionnaire Cohorts B and C [ Time Frame: At baseline and at Week 4 of Cycle 2. ]The European Quality of Life 5D-3L Scale (EQ-5D-3L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. Responses are: '1' = no problem, and '3' = the most serious problem. The responses are combined in a 5-digit number. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility. Baseline evaluations or events are defined as occurring before the date and time of the first dose of study treatment. Evaluations on the same date and time of the first dose of study treatment were considered as baseline evaluations.
- Change From Baseline in Health Status and Health Utility by 3-level EuroQol Five Dimensions (EQ-5D-3L) Questionnaire Cohort D [ Time Frame: At baseline and 4 weeks after first dose. ]The European Quality of Life 5D-3L Scale (EQ-5D-3L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. Responses are: '1' = no problem, and '3' = the most serious problem. The responses are combined in a 5-digit number. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility. Baseline evaluations or events are defined as occurring before the date and time of the first dose of study treatment. Evaluations on the same date and time of the first dose of study treatment were considered as baseline evaluations.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02985957
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| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Documents provided by Bristol-Myers Squibb:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT02985957 |
| Other Study ID Numbers: |
CA209-650 2016-001928-54 ( EudraCT Number ) |
| First Posted: | December 7, 2016 Key Record Dates |
| Results First Posted: | April 24, 2023 |
| Last Update Posted: | April 24, 2023 |
| Last Verified: | April 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases Prednisone Nivolumab |
Ipilimumab Anti-Inflammatory Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents Antineoplastic Agents, Immunological Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |