Prostate CancerPhase 2CheckMate 650NCT02985957
A Study of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer (CheckMate 650)
A Phase 2 study testing Nivolumab, Ipilimumab and Cabazitaxel in people with Prostate Cancer, run by Bristol-Myers Squibb at 59 sites in 10 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Nivolumab, Ipilimumab and Cabazitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 351 participants
- Where
- 59 sitesin 10 countries
- Study dates
- 26 Mar 2017to 7 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
59 sites in 10 countries.
59 sites in 10 countries
United States15 sites
Local Institution - 0078
Albany, New York, 12208
Local Institution - 0047
Allentown, Pennsylvania, 18105
Local Institution - 0079
Austin, Texas, 78731
Local Institution - 0067
Charleston, South Carolina, 29425
Local Institution - 0011
Chicago, Illinois, 60637
Local Institution - 0002
Houston, Texas, 77030
Local Institution - 0065
Lake Success, New York, 11042
Local Institution - 0075
Las Vegas, Nevada, 89169
Local Institution - 0046
Marietta, Georgia, 30060
Local Institution - 0076
Minneapolis, Minnesota, 55404
Local Institution - 0001
New York, New York, 10029
Local Institution - 0010
Philadelphia, Pennsylvania, 19104
Local Institution - 0008
St Louis, Missouri, 63110
Local Institution - 0077
Tigard, Oregon, 97223
Local Institution - 0074
Tucson, Arizona, 85711
Germany12 sites
Local Institution - 0041
Braunschweig, 38114
Local Institution - 0032
Dresden, 01307
Local Institution - 0038
Göttingen, Lower Saxony, 37075
Local Institution - 0019
Herne, 44625
Local Institution - 0017
Jena, 07747
Local Institution - 0034
Munich, 81377
Local Institution - 0018
Münster, 48149
Local Institution - 0037
Nuremberg, 90419
Local Institution - 0042
Nürtingen, 72622
Local Institution - 0036
Rostock, 18107
Local Institution - 0033
Tübingen, 72076
Local Institution - 0035
Wesel, 46483
Australia7 sites
Local Institution - 0031
Clayton, Victoria, 3168
Local Institution - 0030
Elizabeth Vale, South Australia, 5112
Local Institution - 0027
Gosford, New South Wales, 2250
Local Institution - 0028
Southport, Queensland, 4215
Local Institution - 0059
Wahroonga, New South Wales, 2076
Local Institution - 0029
Westmead, New South Wales, 2145
Local Institution - 0043
Woolloongabba, Queensland, 4012
Spain7 sites
Local Institution - 0026
Badajoz, 06006
Local Institution - 0025
Barcelona, 08003
Local Institution - 0022
Madrid, Sede Madrid, 28027
Local Institution - 0020
Madrid, 28007
Local Institution - 0021
Madrid, 28041
Local Institution - 0024
Málaga, 29010
Local Institution - 0023
Santiago Compostela, 15706
Italy5 sites
Local Institution - 0071
Arezzo, 52100
Local Institution - 0052
Milan, 20133
Local Institution - 0053
Naples, 80131
Local Institution - 0072
Parma, 43100
Local Institution - 0051
Terni, 05100
Denmark4 sites
Local Institution - 0062
Aalborg, 9000
Local Institution - 0063
Aarhus N, Central Jutland, 8200
Local Institution - 0061
København Ø, 2100
Local Institution - 0060
Odense, 5000
France4 sites
Local Institution - 0009
Clermont-Ferrand, 63000
Local Institution - 0005
Lyon, 69008
Local Institution - 0004
Marseille, 13273
Local Institution - 0003
Villejuif, 94805
Poland3 sites
Local Institution - 0066
Koszalin, 75-581
Local Institution - 0055
Krakow, Lesser Poland Voivodeship, 30-688
Local Institution - 0054
Warsaw, 02-781
About this study
Official title: A Phase 2 Trial of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer
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).
- Conditions
- Prostate Cancer
- Being tested
- Nivolumab, Ipilimumab, Cabazitaxel, Prednisone
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
Also called BMS-936558, Opdivo
Specified dose on specified days
IpilimumabBiological
Also called BMS-734016, Yervoy
Specified dose on specified days
CabazitaxelDrug
Specified dose on specified days
PrednisoneDrug
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (Arm A) | Experimental | Not described Receives: Biological: Nivolumab; Biological: Ipilimumab |
| Cohort B (Arm B) | Experimental | Not described Receives: Biological: Nivolumab; Biological: Ipilimumab |
| Cohort C (Arm C) | Experimental | Not described Receives: Biological: Nivolumab; Biological: Ipilimumab |
| Cohort D (Arm D1) | Experimental | Not described Receives: Biological: Nivolumab; Biological: Ipilimumab |
| Cohort D (Arm D2) | Experimental | Not described Receives: Biological: Nivolumab; Biological: Ipilimumab |
| Cohort D (Arm D3) | Experimental | Not described Receives: Biological: Ipilimumab |
| Cohort D (Arm D4) | Experimental | Not described Receives: Drug: Cabazitaxel; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) Cohorts B and C Per BICR
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.
Measured: 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) Cohort D
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.
Measured: 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)
Radiographic Progression Free Survival (rPFS) for Cohorts B and C Per BICR
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
- 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.
Measured: 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) for Cohort D
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.
Measured: From randomization and the first date of documented progression or death due to any cause, whichever occurs first (assessed up to approximately 61 months)
Secondary outcomes (27)
Radiographic/Clinical Progression Free Survival (rcPFS) for Cohorts B and C
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.
Measured: 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
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.
Measured: 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
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.
Measured: From first dose to the date of death due to any cause (assessed up to approximately 61 months)
Overall Survival (OS) Cohort D
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Death due to any cause.
Measured: 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
Death due to any cause.
Measured: 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
The number of participants with a change in laboratory values from baseline Grade in Cohorts A, B and C.
Measured: 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 Changes in Laboratory Values From Baseline in Cohort D
The number of participants with an change in laboratory values from baseline Grade in Cohort D.
Measured: 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
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
Measured: 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
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
Measured: 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 Thyroid Function Laboratory Abnormalities in Cohort A, B and C
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
Measured: 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
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
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: At baseline and 4 weeks after first dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2016 (estimated)
- Study start26 Mar 2017
- Primary completion5 Apr 2022
- Study completion7 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 351 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02985957
- Sponsor's protocol ID
- CA209-650
- Other IDs
- 2016-001928-54, 2016
- Acronym
- CheckMate 650
- Status last verified
- Dec 2025
- First submitted
- 22 Nov 2016
- Last updated
- 22 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sharma P, Pachynski RK, Narayan V, Flechon A, Gravis G, Galsky MD, Mahammedi H, Patnaik A, Subudhi SK, Ciprotti M, Simsek B, Saci A, Hu Y, Han GC, Fizazi K. Nivolumab Plus Ipilimumab for Metastatic Castration-Resistant Prostate Cancer: Preliminary Analysis of Patients in the CheckMate 650 Trial. Cancer Cell. 2020 Oct 12;38(4):489-499.e3. doi: 10.1016/j.ccell.2020.08.007. Epub 2020 Sep 10.
PubMed 32916128
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02985957
- Acronym / sponsor ID
- CheckMate 650 / CA209-650
- Conditions
- Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 351 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 26 Mar 2017 (actual)
- Primary completion
- 5 Apr 2022 (actual)
- Study completion
- 7 Jan 2025 (actual)
- First posted
- 7 Dec 2016 (estimated)
- Results
- Posted 24 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort A (Arm A) | Experimental | Biological: Nivolumab, Biological: Ipilimumab |
| Cohort B (Arm B) | Experimental | Biological: Nivolumab, Biological: Ipilimumab |
| Cohort C (Arm C) | Experimental | Biological: Nivolumab, Biological: Ipilimumab |
| Cohort D (Arm D1) | Experimental | Biological: Nivolumab, Biological: Ipilimumab |
| Cohort D (Arm D2) | Experimental | Biological: Nivolumab, Biological: Ipilimumab |
| Cohort D (Arm D3) | Experimental | Biological: Ipilimumab |
| Cohort D (Arm D4) | Experimental | Drug: Cabazitaxel, Drug: Prednisone |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
- 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
Key exclusion criteria (8 listed)
- 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
- Prior radiation therapy within 14 days prior to first dose of nivolumab combined with ipilimumab
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: BMS-936558, OpdivoSpecified dose on specified days | Biological | Cohort A (Arm A), Cohort B (Arm B), Cohort C (Arm C), Cohort D (Arm D1), Cohort D (Arm D2) |
| IpilimumabAlso: BMS-734016, YervoySpecified dose on specified days | Biological | Cohort A (Arm A), Cohort B (Arm B), Cohort C (Arm C), Cohort D (Arm D1), Cohort D (Arm D2), Cohort D (Arm D3) |
| CabazitaxelSpecified dose on specified days | Drug | Cohort D (Arm D4) |
| PrednisoneSpecified dose on specified days | Drug | Cohort D (Arm D4) |
Primary outcome
Objective Response Rate (ORR) Cohorts B and C Per BICR
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 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.
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 Per BICR
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 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.
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 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.
27 secondary outcomes
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) 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 93 months)
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) Cohort D
Time frame: 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
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)
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 93 months)
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)
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 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
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 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 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
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 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 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
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)
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 8.48 months assessed up to approximately 29.09 months)
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).
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 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
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 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 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
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 Liver Function Laboratory Abnormalities in Cohort D
Time frame: 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 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 Thyroid Function Laboratory Abnormalities in Cohort D
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At baseline and 4 weeks after first dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32916128Sharma P, Pachynski RK, Narayan V, Flechon A, Gravis G, Galsky MD, Mahammedi H, Patnaik A, Subudhi SK, Ciprotti M, Simsek B, Saci A, Hu Y, Han GC, Fizazi K. Nivolumab Plus Ipilimumab for Metastatic Castration-Resistant Prostate Cancer: Preliminary Analysis of Patients in the CheckMate 650 Trial. Cancer Cell. 2020 Oct 12;38(4):489-499.e3. doi: 10.1016/j.ccell.2020.08.007. Epub 2020 Sep 10.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
59 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, Ipilimumab and Cabazitaxel in people with Prostate Cancer, run by Bristol-Myers Squibb at 59 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 59 sites in United States, Germany, Australia, Spain, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) Cohorts B and C Per BICR (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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02985957, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.