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
2 other identifiers
interventional
821
23 countries
163
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2012
Longer than P75 for phase_3
163 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 16, 2012
CompletedFirst Posted
Study publicly available on registry
August 20, 2012
CompletedStudy Start
First participant enrolled
October 9, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 6, 2015
CompletedResults Posted
Study results publicly available
April 29, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
July 19, 2021
CompletedAugust 9, 2022
July 1, 2022
2.6 years
August 16, 2012
March 28, 2016
July 15, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (9)
Investigator-assessed Objective Response Rate (ORR)
from randomization up to disease progression or death (approximately up to 105 Months)
Investigator-assessed Duration of Objective Response
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
Randomization to date of first response (approximately 105 months)
Investigator-assessed Time of Progression-free Survival (PFS)
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
Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months)
- +4 more secondary outcomes
Study Arms (2)
Arm 1: Nivolumab
EXPERIMENTALNivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Arm 2: Everolimus
ACTIVE COMPARATOREverolimus 10 mg tablets by mouth daily until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Interventions
Eligibility Criteria
You may qualify if:
- 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%
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bristol-Myers Squibblead
- Ono Pharmaceutical Co. Ltdcollaborator
Study Sites (168)
Local Institution - 0182
Fayetteville, Arkansas, 72703, United States
UCSD Moores Cancer Center
La Jolla, California, 92093-0698, United States
Local Institution - 0024
Los Angeles, California, 90033, United States
University Of Southern California
Los Angeles, California, 90033, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Ucsf Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115, United States
Stanford Cancer Institute
Stanford, California, 94305, United States
University Of Colorado
Aurora, Colorado, 80045, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
Local Institution - 0027
Washington D.C., District of Columbia, 20007, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612-9497, United States
Winship Cancer Institute.
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
Loyola University Chicago
Maywood, Illinois, 60153, United States
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202, United States
University Of Iowa Hospitals And Clinics
Iowa City, Iowa, 52242, United States
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
Baltimore, Maryland, 21231-1000, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
University Of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-5946, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Nassau
New York, New York, 10065, United States
Weill Cornell Medical College
New York, New York, 10065, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
The Ohio State University
Columbus, Ohio, 43210, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Temple University Hospital
Philadelphia, Pennsylvania, 19140, United States
Medical University Of South Carolina
Charleston, South Carolina, 29425, United States
St Francis Hospital
Greenville, South Carolina, 29601, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-6307, United States
Ut Southwestern Medical Center
Dallas, Texas, 75390-9133, United States
Local Institution - 0139
Houston, Texas, 77030-4009, United States
CTRC at UTHSC San Antonio
San Antonio, Texas, 78229, United States
Local Institution - 0076
Richmond, Virginia, 23229, United States
Local Institution - 0009
Seattle, Washington, 98109, United States
University Of Washington
Seattle, Washington, 98109, United States
COIBA
Berazategui, Buenos Aires, 1880, Argentina
Local Institution
Capital Federal, Buenos Aires, 1431, Argentina
Centro Para La Atencion Integral Del Paciente Oncologico
San Miguel de Tucumán, Tucumán Province, 4000, Argentina
Local Institution
Buenos Aires, C1280AEB, Argentina
Local Institution
Buenos Aires, C1426ANZ, Argentina
Instituto Oncologico De Cordoba
Córdoba, X5006HBF, Argentina
Local Institution - 0095
Westmead, New South Wales, 2145, Australia
Local Institution
Woodville South, South Australia, 5011, Australia
Local Institution
Box Hill, Victoria, 3128, Australia
Local Institution
Clayton, Victoria, 3168, Australia
Local Institution
Melbourne, Victoria, 3000, Australia
Local Institution
Linz, 4020, Austria
Local Institution
Vienna, 1090, Austria
Local Institution
Vienna, 1130, Austria
Local Institution
Brussels, 1090, Belgium
Local Institution
Brussels, 1200, Belgium
Local Institution
Ghent, 9000, Belgium
Local Institution
Leuven, 3000, Belgium
Local Institution - 0125
Ijuí, Rio Grande do Sul, 98700-000, Brazil
Local Institution - 0124
São Paulo, 01246-000, Brazil
Local Institution
São Paulo, 01321-001, Brazil
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
BC Cancer Agency - Vancouver Centre
Vancouver, British Columbia, V5Z 4E6, Canada
Centre D'Oncologie Dr-Leon-Richard
Moncton, New Brunswick, E1C 8X3, Canada
QEII Health Sciences Centre
Halfax, Nova Scotia, B3H 2Y9, Canada
Local Institution - 0143
Oshawa, Ontario, L1G 2B9, Canada
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Chum, Hopital Notre-Dame
Montreal, Quebec, H2L 4M1, Canada
Local Institution - 0145
Montreal, H3T 1E2, Canada
Local Institution
Hradec Králové, 500 05, Czechia
Local Institution
Olomouc, 779 00, Czechia
Local Institution
Prague, 150 06, Czechia
Local Institution
Aarhus N, 8200, Denmark
Local Institution
Herlev, 2730, Denmark
Local Institution - 0137
Odense, 5000, Denmark
Local Institution
Helsinki, 00029, Finland
Local Institution - 0006
Vandœuvre-lès-Nancy, Lorraine, 54519, France
Local Institution - 0008
Bordeaux, 33075, France
Local Institution
Bordeaux, 33075, France
Local Institution - 0007
Lyon, 69373, France
Local Institution
Lyon, 69373, France
Local Institution - 0004
Marseille, 13009, France
Local Institution
Marseille, 13009, France
Local Institution - 0118
Paris, 75908, France
Local Institution - 0003
Poitiers, 86000, France
Local Institution
Poitiers, 86000, France
Local Institution - 0005
Saint-Herblain, 44805, France
Local Institution
Saint-Herblain, 44805, France
Local Institution - 0012
Toulouse, 31059, France
Local Institution
Toulouse, 31059, France
Local Institution
Vandœuvre-lès-Nancy, 54511, France
Local Institution - 0002
Villejuif, 94805, France
Local Institution
Villejuif, 94805, France
Local Institution
Aachen, 52074, Germany
Local Institution
Dresden, 01307, Germany
Local Institution
Erlangen, 91054, Germany
Local Institution
Essen, 45122, Germany
Local Institution
Hanover, 30625, Germany
Local Institution - 0126
Heidelberg, 69120, Germany
Local Institution
Munich, 81675, Germany
Local Institution
Tübingen, 72076, Germany
Alexandra General Hospital Of Athens
Athens, 12462, Greece
Euromedica General Clinic of Thessaloniki
Thessaloniki, 54645, Greece
Local Institution
Tallaght, Dublin, DUBLIN 24, Ireland
Local Institution - 0087
Dublin, 7, Ireland
Local Institution
Dublin, Dublin 7, Ireland
Local Institution
Haifa, 31096, Israel
Local Institution - 0148
Petah Tikva, 49100, Israel
Local Institution
Ramat Gan, 52621, Israel
Local Institution
Tel Aviv, 64239, Israel
Local Institution
Arezzo, 52100, Italy
Local Institution
Meldola (fc), 47014, Italy
Local Institution - 0082
Milan, 20133, Italy
Local Institution
Rimini, 47900, Italy
Local Institution
Roma, 00144, Italy
Local Institution
Roma, 00152, Italy
Local Institution - 0102
Rozzano, 20089, Italy
Local Institution
Siena, 53100, Italy
Local Institution
Terni, 05100, Italy
Local Institution
Akita, Akita, 0108543, Japan
Local Institution
Chiba, Chiba, 2608717, Japan
Local Institution
Higashiku, Fukuoka, 812-8582, Japan
Local Institution
Sapporo, Hokkaido, 0608543, Japan
Local Institution
Sapporo, Hokkaido, 0608648, Japan
Local Institution
Morioka, Iwate, 0208505, Japan
Local Institution
Yokohama, Kanagawa, 2360004, Japan
Local Institution
Kyoto, Kyoto, 602-8566, Japan
Local Institution
Osaka-sayama-shi, Osaka, 5898511, Japan
Local Institution - 0169
Suita, Osaka, 5650871, Japan
Local Institution - 0167
Hamamatsu, Shizuoka, 4313192, Japan
Local Institution
Tokushima, Tokushima, 7708503, Japan
Local Institution
Yamagata, Yamagata, 9909585, Japan
Local Institution
Kobe-city, Hyogo, 650-0017, Japan
Local Institution
Kumamoto, 860-8556, Japan
Local Institution
Tokyo, 1138603, Japan
Local Institution
Tokyo, 1138655, Japan
Local Institution
Tokyo, 1358550, Japan
Local Institution
Tokyo, 1608582, Japan
Local Institution
Tokyo, 1628666, Japan
Local Institution
Tokyo, 1738606, Japan
Local Institution
Bergen, 5021, Norway
Local Institution
Lorenskog, 1478, Norway
Local Institution
Gdansk, 80-219, Poland
Local Institution
Lodz, 93-513, Poland
Local Institution
Poznan, 60-569, Poland
Local Institution
Rybnik, 44-200, Poland
Local Institution
Warsaw, 00-909, Poland
Local Institution
Wroclaw, 50-556, Poland
Local Institution
Bucharest, 022328, Romania
Local Institution
Craiova, 200385, Romania
Local Institution
Iași, 700106, Romania
Local Institution
Timișoara, 300167, Romania
Local Institution
Moscow, 115478, Russia
Local Institution
Moscow, 121309, Russia
Local Institution
Saint Petersburg, 198255, Russia
Local Institution
Pamplona, Navarre, 31008, Spain
Local Institution
Barcelona, 08035, Spain
Local Institution - 0064
L'Hospitalet de Llobregat, 08907, Spain
Local Institution
Madrid, 28007, Spain
Local Institution
Madrid, 28040, Spain
Local Institution
Madrid, 28041, Spain
Local Institution
Gothenberg, 413 45, Sweden
Local Institution
Solna, 171 64, Sweden
Local Institution
Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
Local Institution - 0048
Swansea, Carmarthenshire, SA2 8QA, United Kingdom
Local Institution
Swansea, Carmarthenshire, SA2 8QA, United Kingdom
Local Institution
London, Greater London, HA6 2RN, United Kingdom
Local Institution
London, Greater London, SW3 6JJ, United Kingdom
Related Publications (8)
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.
PMID: 33428174DERIVEDAmbavane 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.
PMID: 31992108DERIVEDShah 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.
PMID: 31272883DERIVEDLong 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.
PMID: 30215677DERIVEDEscudier 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.
PMID: 28410865DERIVEDEscudier 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.
PMID: 28262413DERIVEDCella 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.
PMID: 27283863DERIVEDMotzer 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.
PMID: 26406148DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
August 16, 2012
First Posted
August 20, 2012
Study Start
October 9, 2012
Primary Completion
May 6, 2015
Study Completion
July 19, 2021
Last Updated
August 9, 2022
Results First Posted
April 29, 2016
Record last verified: 2022-07