Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)

A Randomized, Open-Label, Phase 3 Study of Nivolumab (BMS-936558) vs. Everolimus in Subjects With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy

The purpose of the study is to compare the clinical benefit, as measured by duration of overall survival, of Nivolumab vs. Everolimus in subjects with advanced or metastatic clear-cell renal cell carcinoma who have received prior anti-angiogenic therapy

Study Overview

• Status: Completed
• Conditions: Advanced or Metastatic (Medically or Surgically Unresectable) Clear-cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Everolimus; Biological: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 821
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Local Institution
  • Buenos Aires, Argentina, C1426ANZ
    • Local Institution
  • Cordoba, Argentina, X5006HBF
    • Instituto Oncologico de Cordoba
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, 1880
      • COIBA
    • Capital Federal, Buenos Aires, Argentina, 1431
      • Local Institution
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, 4000
      • Centro para la Atención Integral del paciente Oncológico
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0095
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Local Institution
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Local Institution
    • Clayton, Victoria, Australia, 3168
      • Local Institution
    • Melbourne, Victoria, Australia, 3000
      • Local Institution
• Austria
  • Linz, Austria, 4020
    • Local Institution
  • Wien, Austria, 1090
    • Local Institution
  • Wien, Austria, 1130
    • Local Institution
• Belgium
  • Brussels, Belgium, 1090
    • Local Institution
  • Bruxelles, Belgium, 1200
    • Local Institution
  • Gent, Belgium, 9000
    • Local Institution
  • Leuven, Belgium, 3000
    • Local Institution
• Brazil
  • Sao Paulo, Brazil, 01321-001
    • Local Institution
  • Sao Paulo, Brazil, 01246-000
    • Local Institution - 0124
  • RIO Grande DO SUL
    • Ijui, RIO Grande DO SUL, Brazil, 98700-000
      • Local Institution - 0125
• Canada
  • Montreal, Canada, H3T 1E2
    • Local Institution - 0145
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency - Vancouver Centre
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Centre D'Oncologie Dr-Leon-Richard
  • Nova Scotia
    • Halfax, Nova Scotia, Canada, B3H 2Y9
      • QEII Health Sciences Centre
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Local Institution - 0143
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Chum, Hopital Notre-Dame
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Local Institution
  • Olomouc, Czechia, 779 00
    • Local Institution
  • Prague 5, Czechia, 150 06
    • Local Institution
• Denmark
  • Aarhus N, Denmark, 8200
    • Local Institution
  • Herlev, Denmark, 2730
    • Local Institution
  • Odense, Denmark, 5000
    • Local Institution - 0137
• Finland
  • Helsinki, Finland, 00029
    • Local Institution
• France
  • Bordeaux, France, 33075
    • Local Institution
  • Bordeaux, France, 33075
    • Local Institution - 0008
  • Lyon Cedex, France, 69373
    • Local Institution - 0007
  • Lyon Cedex, France, 69373
    • Local Institution
  • Marseille Cedex 9, France, 13009
    • Local Institution
  • Marseille Cedex 9, France, 13009
    • Local Institution - 0004
  • Paris, France, 75908
    • Local Institution - 0118
  • Poitiers, France, 86000
    • Local Institution
  • Poitiers, France, 86000
    • Local Institution - 0003
  • Saint Herblain Cedex, France, 44805
    • Local Institution - 0005
  • Saint Herblain Cedex, France, 44805
    • Local Institution
  • Toulouse Cedex 9, France, 31059
    • Local Institution
  • Toulouse Cedex 9, France, 31059
    • Local Institution - 0012
  • Vandoeuvre Les Nancy, France, 54511
    • Local Institution
  • Villejuif Cedex, France, 94805
    • Local Institution
  • Villejuif Cedex, France, 94805
    • Local Institution - 0002
  • Lorraine
    • Vandoeuvre-lès-Nancy, Lorraine, France, 54519
      • Local Institution - 0006
• Germany
  • Aachen, Germany, 52074
    • Local Institution
  • Dresden, Germany, 01307
    • Local Institution
  • Erlangen, Germany, 91054
    • Local Institution
  • Essen, Germany, 45122
    • Local Institution
  • Hannover, Germany, 30625
    • Local Institution
  • Heidelberg, Germany, 69120
    • Local Institution - 0126
  • Munich, Germany, 81675
    • Local Institution
  • Tuebingen, Germany, 72076
    • Local Institution
• Greece
  • Athens, Greece, 12462
    • Alexandra General Hospital of Athens
  • Thessaloniki, Greece, 54645
    • EUROMEDICA General Clinic of Thessaloniki
• Ireland
  • Dublin, Ireland, DUBLIN 7
    • Local Institution
  • Dublin, Ireland, 7
    • Local Institution - 0087
  • Dublin
    • Tallaght, Dublin, Ireland, DUBLIN 24
      • Local Institution
• Israel
  • Haifa, Israel, 31096
    • Local Institution
  • Petah Tikva, Israel, 49100
    • Local Institution - 0148
  • Ramat-gan, Israel, 52621
    • Local Institution
  • Tel Aviv, Israel, 64239
    • Local Institution
• Italy
  • Arezzo, Italy, 52100
    • Local Institution
  • Meldola (fc), Italy, 47014
    • Local Institution
  • Milano, Italy, 20133
    • Local Institution - 0082
  • Rimini, Italy, 47900
    • Local Institution
  • Roma, Italy, 00144
    • Local Institution
  • Roma, Italy, 00152
    • Local Institution
  • Rozzano, Italy, 20089
    • Local Institution - 0102
  • Siena, Italy, 53100
    • Local Institution
  • Terni, Italy, 05100
    • Local Institution
• Japan
  • Kobe-city, Hyogo, Japan, 650-0017
    • Local Institution
  • Kumamoto, Japan, 860-8556
    • Local Institution
  • Tokyo, Japan, 1738606
    • Local Institution
  • Tokyo, Japan, 1138603
    • Local Institution
  • Tokyo, Japan, 1138655
    • Local Institution
  • Tokyo, Japan, 1358550
    • Local Institution
  • Tokyo, Japan, 1608582
    • Local Institution
  • Tokyo, Japan, 1628666
    • Local Institution
  • Akita
    • Akita-shi, Akita, Japan, 0108543
      • Local Institution
  • Chiba
    • Chiba-shi, Chiba, Japan, 2608717
      • Local Institution
  • Fukuoka
    • Higashi-ku, Fukuoka, Japan, 812-8582
      • Local Institution
  • Hokkaido
    • Sapporo-city, Hokkaido, Japan, 0608543
      • Local Institution
    • Sapporo-shi, Hokkaido, Japan, 0608648
      • Local Institution
  • Iwate
    • Morioka-shi, Iwate, Japan, 0208505
      • Local Institution
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2360004
      • Local Institution
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • Local Institution
  • Osaka
    • Osaka-sayama-shi, Osaka, Japan, 5898511
      • Local Institution
    • Suita, Osaka, Japan, 5650871
      • Local Institution - 0169
  • Shizuoka
    • Hamamatsu-shi, Shizuoka, Japan, 4313192
      • Local Institution - 0167
  • Tokushima
    • Tokushima-shi, Tokushima, Japan, 7708503
      • Local Institution
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 9909585
      • Local Institution
• Norway
  • Bergen, Norway, 5021
    • Local Institution
  • Lorenskog, Norway, 1478
    • Local Institution
• Poland
  • Gdansk, Poland, 80-219
    • Local Institution
  • Lodz, Poland, 93-513
    • Local Institution
  • Poznan, Poland, 60-569
    • Local Institution
  • Rybnik, Poland, 44-200
    • Local Institution
  • Warszawa, Poland, 00-909
    • Local Institution
  • Wroclaw, Poland, 50-556
    • Local Institution
• Romania
  • Bucharest, Romania, 022328
    • Local Institution
  • Craiova, Romania, 200385
    • Local Institution
  • Iasi, Romania, 700106
    • Local Institution
  • Timisoara, Romania, 300167
    • Local Institution
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Local Institution
  • Moscow, Russian Federation, 121309
    • Local Institution
  • St Petersburg, Russian Federation, 198255
    • Local Institution
• Spain
  • Barcelona, Spain, 08035
    • Local Institution
  • Hospitalet De Llobregat, Spain, 08907
    • Local Institution - 0064
  • Madrid, Spain, 28041
    • Local Institution
  • Madrid, Spain, 28007
    • Local Institution
  • Madrid, Spain, 28040
    • Local Institution
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Local Institution
• Sweden
  • Gothenberg, Sweden, 413 45
    • Local Institution
  • Solna, Sweden, 171 64
    • Local Institution
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Local Institution
  • Carmarthenshire
    • Swansea, Carmarthenshire, United Kingdom, SA2 8QA
      • Local Institution - 0048
    • Swansea, Carmarthenshire, United Kingdom, SA2 8QA
      • Local Institution
  • Greater London
    • London, Greater London, United Kingdom, SW3 6JJ
      • Local Institution
    • London, Greater London, United Kingdom, HA6 2RN
      • Local Institution
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Local Institution - 0182
  • California
    • La Jolla, California, United States, 92093-0698
      • UCSD Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • Local Institution - 0024
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • Stanford, California, United States, 94305
      • Stanford Cancer Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20007
      • Local Institution - 0027
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center & Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute.
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University Of Iowa Hospitals And Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21231-1000
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5946
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Nassau
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29601
      • St Francis Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37232-6307
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-9133
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030-4009
      • Local Institution - 0139
    • San Antonio, Texas, United States, 78229
      • CTRC at UTHSC San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Local Institution - 0076
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 0009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men & women ≥18 years of age
• Histologic confirmation of renal cell carcinoma (RCC) with clear-cell component
• Advanced/metastatic RCC
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Received 1 or 2 prior anti-angiogenic therapy regimens in advanced or metastatic setting
• No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting, and evidence of progression on or after last treatment regimen received and within 6 months of enrollment
• Karnofsky Performance Score ≥70%

Exclusion Criteria:

• Any Central Nervous System (CNS) metastases or history of CNS metastases
• Prior therapy with an Mammalian target of rapamycin (mTOR) inhibitor
• Any active known or suspected autoimmune disease
• Uncontrolled adrenal insufficiency
• Active chronic liver disease
• Prior malignancy active within past 3 years, except for locally curable cancers

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Nivolumab; Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Biological: Nivolumab; Other Names: BMS-936558
Active Comparator: Arm 2: Everolimus; Everolimus 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Drug: Everolimus; Other Names: Afinitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) at Primary Endpoint	Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Interim analysis for the Primary Endpoint occurred after 398 deaths (70% of the total OS events needed for final analysis). At that time the data monitoring committee noted that the pre-specified boundary for OS (nominal significance level p < 0.0148) was crossed while no new safety signals that would affect continuation of the study were found. The study was stopped early by the Sponsor, Bristol-Myers Squibb (BMS) and the interim analysis became the final analysis. As a result, participants in the everolimus groups could be assessed for a crossover to nivolumab treatment if they met all inclusion criteria.	Randomization until 398 deaths, up to May 2015 (approximately 30 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Objective Response Rate (ORR)	ORR is defined as Percentage of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference. Tumor assessments began at 8 weeks following randomization and continued every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or death. CIs used Clopper and Pearson.	from randomization up to disease progression or death (approximately up to 105 Months)
Investigator-assessed Duration of Objective Response	Duration of objective response is defined as the time from study start date to response, CR or partial response, PR) to the date of the first documented tumor progression as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. For participants who neither progress nor die, the duration of objective response were censored at the same time they were censored for the primary definition. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference. Based on Kaplan-Meier Estimates.	From randomization to date of disease progression or death or censoring if no progression or death occurred (approximately 105 months)
Investigator-assessed Time to Objective Response	Time to objective response is defined as the time from randomization to first response (complete response, CR or partial response, PR). CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference.	Randomization to date of first response (approximately 105 months)
Investigator-assessed Time of Progression-free Survival (PFS)	PFS=time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. Participants who die without a reported prior progression and without subsequent anti-cancer therapy were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the date they were randomized. Participants who received any subsequent anti-cancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation date of the subsequent anti-cancer therapy. Progressive disease: >=20% increase in sum of target lesion diameters and sum must show absolute increase of >=5mm; smallest sum on study as reference. Based on Kaplan-Meier Estimates.	from randomization up to disease progression or death (approximately up to 105 Months)
Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level	Quantifiable PD-L1 expression=percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay. If the PD-L1 staining could not be quantified it was classified as: indeterminate=tumor cell membrane staining hampered for reasons attributed to biology of tumor biopsy specimen and not due to improper sample preparation or handling; not evaluable=tumor biopsy specimen was not optimally collected or prepared. Not evaluable determined from H&E process before the tumor biopsy specimen was sent for evaluation or from H&E process during PD-L1 evaluation; baseline PD-L1 expression=if more than one tumor biopsy specimen was available, the most recently collected specimen with a quantifiable result. If all specimens for a given participant are either indeterminate or not evaluable, then the PD-L1 expression was considered indeterminate as long as at least one specimen is indeterminate. Otherwise, PD-L1 expression was considered not evaluable.	Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months)
Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events	Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.	Day of first dose to 30 days post study completion (approximately 106 months)
Percentage of Participants With Disease-related Symptom Progression (DRSP)	Disease-related symptom progression rate (DRSPR)=a decrease of two points in the Functional Assessment of Cancer Therapy-Kidney Symptom Index - Disease Related Symptoms (FKSI-DRS) questionnaire relative to the participant's baseline FKSI-DRS score with no later increase above this threshold observed during the course of the study. The 9 items of the FKSI-DRS were summarized into a symptom scale ranging in score from 0 to 36, with 0 being the worst possible score and 36 being the best possible score. A single measure reporting a decrease of at least 2 units was considered disease-related symptom progression only if it was the last one available for the participant. In order to consider a questionnaire received as valid, over 50% of the items were to be completed. Calculated by the Clopper-Pearson method for each treatment group.	from randomization up to disease progression or death (approximately up to 105 Months)
Number of Participants Meeting Marked Laboratory Abnormality Criteria in Specific Liver and Thyroid Tests	Aspartate aminotransferase, AST. Alanine aminotransaminase, ALT. Total bilirubin, tBIL. Thyroid stimulating hormone, TSH. Upper limit of normal (ULN). Units per Liter (U/L). Results reported in International System of Units (SI).	Day 1 to 30 days post study completion (approximately 106 months)
Number of Participants With Abnormal Hematology and Serum Chemistry Laboratory Parameters by Worse CTC Grade - SI Units	Common Terminology Criteria (CTC) version 4.0 in International System of Units (SI); Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Hematology parameters=Hemoglobin (Gr 3: < 8.0 g/dL), Platelet Count (Gr 3: 25.0 -< 50.0*10^9 c/L; Gr 4: < 25.0*10^9 c/L), Leukocyte Count (Gr 3: 1.0 -< 2.0*10^3 c/µL; Gr4: < 1.0*10^3 c/µL), Absolute Lymphocyte Count (Gr 3: 0.2 -< 0.5*10^3 c/µL; Gr 4: < 0.2*10^3 c/µL), Absolute Neutrophil Count (Gr 3: 0.5 - < 1.0*10^3 c/µL; Gr 4: < 0.5*10^3 c/µL). Liver Function parameters=Alkaline Phosphatase (Gr 3: > 5.0 - 20.0 U/L * ULN; Gr 4: > 20.0 U/L * ULN), AST (Gr 3: > 5.0 - 20.0 U/L * ULN; Gr 4: > 20.0 U/L * ULN), ALT (Gr 3: > 5.0 - 20.0 U/L * ULN; Gr 4: > 20.0 U/L * ULN), tBIL (Gr 3: > 3.0 - 10.0 mg/dL * ULN; Gr 4: > 10.0 mg/dL * ULN). Renal parameter=Creatinine (Grade: Gr3: > 3.0 - 6.0 mg/dL *ULN; Gr4: > 6.0 mg/dL *ULN). Cells per microliter (c/µL). Cells per Liter (c/L). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL).	Day 1 to 30 days post study completion (approximately 106 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd

Publications and helpful links

General Publications

• Long GV, Tykodi SS, Schneider JG, Garbe C, Gravis G, Rashford M, Agrawal S, Grigoryeva E, Bello A, Roy A, Rollin L, Zhao X. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol. 2018 Nov 1;29(11):2208-2213. doi: 10.1093/annonc/mdy408.
• Ambavane A, Yang S, Atkins MB, Rao S, Shah A, Regan MM, McDermott DF, Michaelson MD. Clinical and economic outcomes of treatment sequences for intermediate- to poor-risk advanced renal cell carcinoma. Immunotherapy. 2020 Jan;12(1):37-51. doi: 10.2217/imt-2019-0199. Epub 2020 Jan 29.
• Klijn SL, Fenwick E, Kroep S, Johannesen K, Malcolm B, Kurt M, Kiff C, Borrill J. What Did Time Tell Us? A Comparison and Retrospective Validation of Different Survival Extrapolation Methods for Immuno-Oncologic Therapy in Advanced or Metastatic Renal Cell Carcinoma. Pharmacoeconomics. 2021 Mar;39(3):345-356. doi: 10.1007/s40273-020-00989-1. Epub 2021 Jan 11.
• Shah R, Botteman M, Solem CT, Luo L, Doan J, Cella D, Motzer RJ. A Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) Analysis of Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma (aRCC). Clin Genitourin Cancer. 2019 Oct;17(5):356-365.e1. doi: 10.1016/j.clgc.2019.05.010. Epub 2019 May 31.
• Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, Donskov F, Gurney H, Sosman JA, Zalewski PG, Harmenberg U, McDermott DF, Choueiri TK, Richardet M, Tomita Y, Ravaud A, Doan J, Zhao H, Hardy H, George S. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. Eur Urol. 2017 Sep;72(3):368-376. doi: 10.1016/j.eururo.2017.03.037. Epub 2017 Apr 12.
• Escudier B, Sharma P, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Gurney H, Donskov F, Peltola K, Wagstaff J, Gauler TC, Ueda T, Zhao H, Waxman IM, Motzer RJ; CheckMate 025 investigators. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma. Eur Urol. 2017 Dec;72(6):962-971. doi: 10.1016/j.eururo.2017.02.010. Epub 2017 Mar 3. Erratum In: Eur Urol. 2018 Jan 3;:
• Cella D, Grunwald V, Nathan P, Doan J, Dastani H, Taylor F, Bennett B, DeRosa M, Berry S, Broglio K, Berghorn E, Motzer RJ. Quality of life in patients with advanced renal cell carcinoma given nivolumab versus everolimus in CheckMate 025: a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):994-1003. doi: 10.1016/S1470-2045(16)30125-5. Epub 2016 Jun 6. Erratum In: Lancet Oncol. 2016 Jul;17 (7):e270.
• Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2012
• Primary Completion (Actual): May 6, 2015
• Study Completion (Actual): July 19, 2021

Study Registration Dates

• First Submitted: August 16, 2012
• First Submitted That Met QC Criteria: August 16, 2012
• First Posted (Estimate): August 20, 2012

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: July 15, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Everolimus
• Other Study ID Numbers: CA209-025; 2011-005132-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No