A Study of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer (CheckMate 650)

Prostate Cancer Clinical Trial

— CheckMate 650  

Official title:

A Phase 2 Trial of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02985957
• Other study ID #: CA209-650
• Secondary ID: 2016-001928-54
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 26, 2017
• Est. completion date: January 7, 2025

Study information

• Verified date: May 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 351
• Est. completion date: January 7, 2025
• Est. primary completion date: April 5, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• Nivolumab
Specified dose on specified days
• Ipilimumab
Specified dose on specified days

Drug:
• Cabazitaxel
Specified dose on specified days
• Prednisone
Specified dose on specified days

Locations

Country	Name	City	State
Australia	Local Institution - 0031	Clayton	Victoria
Australia	Local Institution - 0030	Elizabeth Vale	South Australia
Australia	Local Institution - 0027	Gosford	New South Wales
Australia	Local Institution - 0028	Southport	Queensland
Australia	Local Institution - 0059	Wahroonga	New South Wales
Australia	Local Institution - 0029	Westmead	New South Wales
Australia	Local Institution - 0043	Woolloongabba	Queensland
Austria	Local Institution - 0048	Wien
Canada	Local Institution - 0044	Montreal	Quebec
Denmark	Local Institution - 0062	Aalborg
Denmark	Local Institution - 0063	Aarhus N	Midtjylland
Denmark	Local Institution - 0061	Kobenhavn O
Denmark	Local Institution - 0060	Odense
France	Local Institution - 0009	Clermont-ferrand
France	Local Institution - 0005	Lyon
France	Local Institution - 0004	Marseille Cedex 9
France	Local Institution - 0003	Villejuif
Germany	Local Institution - 0041	Braunschweig
Germany	Local Institution - 0032	Dresden
Germany	Local Institution - 0038	Göttingen	Niedersachsen
Germany	Local Institution - 0019	Herne
Germany	Local Institution - 0017	Jena
Germany	Local Institution - 0018	Muenster
Germany	Local Institution - 0034	Munich
Germany	Local Institution - 0037	Nuernberg
Germany	Local Institution - 0042	Nuertingen
Germany	Local Institution - 0036	Rostock
Germany	Local Institution - 0033	Tuebingen
Germany	Local Institution - 0035	Wesel
Italy	Local Institution - 0071	Arezzo
Italy	Local Institution - 0052	Milano
Italy	Local Institution - 0053	Napoli
Italy	Local Institution - 0072	Parma
Italy	Local Institution - 0051	Terni
Poland	Local Institution - 0066	Koszalin
Poland	Local Institution - 0055	Kraków	Malopolskie
Poland	Local Institution - 0054	Warszawa
Spain	Local Institution - 0026	Badajoz
Spain	Local Institution - 0025	Barcelona
Spain	Local Institution - 0020	Madrid
Spain	Local Institution - 0021	Madrid
Spain	Local Institution - 0022	Madrid	Sede Madrid
Spain	Local Institution - 0024	Malaga
Spain	Local Institution - 0023	Santiago Compostela
United States	Local Institution - 0078	Albany	New York
United States	Local Institution - 0047	Allentown	Pennsylvania
United States	Local Institution - 0079	Austin	Texas
United States	Local Institution - 0067	Charleston	South Carolina
United States	Local Institution - 0011	Chicago	Illinois
United States	Local Institution - 0002	Houston	Texas
United States	Local Institution - 0065	Lake Success	New York
United States	Local Institution - 0075	Las Vegas	Nevada
United States	Local Institution - 0046	Marietta	Georgia
United States	Local Institution - 0076	Minneapolis	Minnesota
United States	Local Institution - 0001	New York	New York
United States	Local Institution - 0010	Philadelphia	Pennsylvania
United States	Local Institution - 0008	Saint Louis	Missouri
United States	Local Institution - 0077	Tigard	Oregon
United States	Local Institution - 0074	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Denmark,  France,  Germany,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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)
Primary	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.	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)
Primary	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.	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)
Primary	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.	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	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.	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)
Secondary	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.	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	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.	From first dose to the date of death due to any cause (assessed up to approximately 61 months)
Secondary	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.	From randomization to the date of death due to any cause (assessed up to approximately 61 months)
Secondary	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.	From baseline to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months)
Secondary	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.	From baseline to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	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).
Secondary	The Number of Participants Who Died in Cohorts A, B and C	Death due to any cause.	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).
Secondary	The Number of Participants Who Died in Cohort D	Death due to any cause.	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).
Secondary	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.	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)
Secondary	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.	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)
Secondary	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	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)
Secondary	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	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)
Secondary	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	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)
Secondary	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	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)
Secondary	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.	At baseline and Week 4 (Cycle 2)
Secondary	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.	At baseline and 4 weeks after first dose.
Secondary	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.	At baseline and 4 weeks after first dose.
Secondary	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.	At baseline and at Week 4 of Cycle 2.
Secondary	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.	At baseline and 4 weeks after first dose.

External Links

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