Clinical trial NCT02985957: A Study of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer (CheckMate 650)
Official title: A Phase 2 Trial of Nivolumab Plus Ipilimumab, Ipilimumab Alone, or Cabazitaxel in Men With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2016-12-07
Enrollment: 351
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) Cohorts B and C Per BICR
timeFrame: 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)
measure: Objective Response Rate (ORR) Cohort D
timeFrame: 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)
measure: Radiographic Progression Free Survival (rPFS) for Cohorts B and C Per BICR
timeFrame: 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)
measure: Radiographic Progression-Free Survival (rPFS) for Cohort D
timeFrame: 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:
measure: Radiographic/Clinical Progression Free Survival (rcPFS) for Cohorts B and C
timeFrame: 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)
measure: Radiographic/Clinical Progression Free Survival (rcPFS) for Cohort D
timeFrame: From randomization and the first date of documented progression or death due to any cause, whichever occurs first (assessed up to approximately 61 months)
measure: Overall Survival (OS) Cohorts B and C
timeFrame: From first dose to the date of death due to any cause (assessed up to approximately 61 months)
measure: Overall Survival (OS) Cohort D
timeFrame: From randomization to the date of death due to any cause (assessed up to approximately 61 months)
measure: Prostate-Specific Antigen Response Rate (PSA-RR) Cohorts B and C
timeFrame: From baseline to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months)
measure: Prostate-Specific Antigen Response Rate (PSA-RR) Cohort D
timeFrame: From baseline to the date of objectively documented progression or death due to any cause, whichever occurred first (assessed up to approximately 61 months)
measure: The Number of Participants Experiencing Adverse Events (AEs) in Cohorts A, B and C
timeFrame: 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)
measure: The Number of Participants Experiencing Adverse Events (AEs) in Cohort D
timeFrame: 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)
measure: The Number of Participants Experiencing Serious Adverse Events (SAEs) in Cohorts A, B and C
timeFrame: 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)
measure: The Number of Participants Experiencing Serious Adverse Events (SAEs) in Cohort D
timeFrame: 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)
measure: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation in Cohorts A, B and C
timeFrame: 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)
measure: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation in Cohort D
timeFrame: 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)
measure: The Number of Participants Experiencing Immune Mediated Adverse Events in Cohorts A, B and C
timeFrame: 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)
measure: The Number of Participants Experiencing Immune Mediated Adverse Events in Cohort D
timeFrame: 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).
measure: The Number of Participants Who Died in Cohorts A, B and C
timeFrame: 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).
measure: The Number of Participants Who Died in Cohort D
timeFrame: 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).
measure: The Number of Participants With Changes in Laboratory Values From Baseline in Cohorts A, B and C
timeFrame: 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)
measure: The Number of Participants With Changes in Laboratory Values From Baseline in Cohort D
timeFrame: 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)
measure: The Number of Participants With Liver Function Laboratory Abnormalities in Cohorts A, B and C
timeFrame: 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)
measure: The Number of Participants With Liver Function Laboratory Abnormalities in Cohort D
timeFrame: 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)
measure: The Number of Participants With Thyroid Function Laboratory Abnormalities in Cohort A, B and C
timeFrame: 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)
measure: The Number of Participants With Thyroid Function Laboratory Abnormalities in Cohort D
timeFrame: 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)
measure: Changes in Pain Severity as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Scores Cohorts B and C
timeFrame: At baseline and Week 4 (Cycle 2)
measure: Changes in Pain Severity as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Scores Cohort D
timeFrame: At baseline and 4 weeks after first dose.
measure: Change in Cancer-Related Symptoms and Quality of Life (QoL) by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire Cohort D
timeFrame: At baseline and 4 weeks after first dose.
measure: Change From Baseline in Health Status and Health Utility by 3-level EuroQol Five Dimensions (EQ-5D-3L) Questionnaire Cohorts B and C
timeFrame: At baseline and at Week 4 of Cycle 2.
measure: Change From Baseline in Health Status and Health Utility by 3-level EuroQol Five Dimensions (EQ-5D-3L) Questionnaire Cohort D
timeFrame: At baseline and 4 weeks after first dose.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Local Institution - 0074
state: Arizona
city: Marietta
country: United States
facility: Local Institution - 0046
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0011
state: Illinois
city: Minneapolis
country: United States
facility: Local Institution - 0076
state: Minnesota
city: Saint Louis
country: United States
facility: Local Institution - 0008
state: Missouri
city: Las Vegas
country: United States
facility: Local Institution - 0075
state: Nevada
city: Albany
country: United States
facility: Local Institution - 0078
state: New York
city: Lake Success
country: United States
facility: Local Institution - 0065
state: New York
city: New York
country: United States
facility: Local Institution - 0001
state: New York
city: Tigard
country: United States
facility: Local Institution - 0077
state: Oregon
city: Allentown
country: United States
facility: Local Institution - 0047
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0010
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0067
state: South Carolina
city: Austin
country: United States
facility: Local Institution - 0079
state: Texas
city: Houston
country: United States
facility: Local Institution - 0002
state: Texas
city: Gosford
country: Australia
facility: Local Institution - 0027
state: New South Wales
city: Wahroonga
country: Australia
facility: Local Institution - 0059
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution - 0029
state: New South Wales
city: Southport
country: Australia
facility: Local Institution - 0028
state: Queensland
city: Woolloongabba
country: Australia
facility: Local Institution - 0043
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Local Institution - 0030
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 0031
state: Victoria
city: Wien
country: Austria
facility: Local Institution - 0048
city: Montreal
country: Canada
facility: Local Institution - 0044
state: Quebec
city: Aarhus N
country: Denmark
facility: Local Institution - 0063
state: Midtjylland
city: Aalborg
country: Denmark
facility: Local Institution - 0062
city: Kobenhavn O
country: Denmark
facility: Local Institution - 0061
city: Odense
country: Denmark
facility: Local Institution - 0060
city: Clermont-ferrand
country: France
facility: Local Institution - 0009
city: Lyon
country: France
facility: Local Institution - 0005
city: Marseille Cedex 9
country: France
facility: Local Institution - 0004
city: Villejuif
country: France
facility: Local Institution - 0003
city: Göttingen
country: Germany
facility: Local Institution - 0038
state: Niedersachsen
city: Braunschweig
country: Germany
facility: Local Institution - 0041
city: Dresden
country: Germany
facility: Local Institution - 0032
city: Herne
country: Germany
facility: Local Institution - 0019
city: Jena
country: Germany
facility: Local Institution - 0017
city: Muenster
country: Germany
facility: Local Institution - 0018
city: Munich
country: Germany
facility: Local Institution - 0034
city: Nuernberg
country: Germany
facility: Local Institution - 0037
city: Nuertingen
country: Germany
facility: Local Institution - 0042
city: Rostock
country: Germany
facility: Local Institution - 0036
city: Tuebingen
country: Germany
facility: Local Institution - 0033
city: Wesel
country: Germany
facility: Local Institution - 0035
city: Arezzo
country: Italy
facility: Local Institution - 0071
city: Milano
country: Italy
facility: Local Institution - 0052
city: Napoli
country: Italy
facility: Local Institution - 0053
city: Parma
country: Italy
facility: Local Institution - 0072
city: Terni
country: Italy
facility: Local Institution - 0051
city: Kraków
country: Poland
facility: Local Institution - 0055
state: Małopolskie
city: Koszalin
country: Poland
facility: Local Institution - 0066
city: Warszawa
country: Poland
facility: Local Institution - 0054
city: Madrid
country: Spain
facility: Local Institution - 0022
state: Sede Madrid
city: Badajoz
country: Spain
facility: Local Institution - 0026
city: Barcelona
country: Spain
facility: Local Institution - 0025
city: Madrid
country: Spain
facility: Local Institution - 0020
city: Madrid
country: Spain
facility: Local Institution - 0021
city: Malaga
country: Spain
facility: Local Institution - 0024
city: Santiago Compostela
country: Spain
facility: Local Institution - 0023
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.