Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)

A Phase 3, Randomized, Open-Label Study of Nivolumab Combined With Ipilimumab Versus Sunitinib Monotherapy in Subjects With Previously Untreated, Advanced or Metastatic Renal Cell Carcinoma

The purpose of this study is to compare the objective response rate, progression free survival and the overall survival of Nivolumab combined with Ipilimumab to Sunitinib monotherapy in patients with previously untreated Renal Cell Cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Renal Cell Carcinoma; Advanced Renal Cell Carcinoma
• Intervention / Treatment: Biological: Nivolumab; Drug: Sunitinib; Biological: Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 1096
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, 1426
    • Local Institution - 0097
  • Córdoba, Argentina, 5000
    • Local Institution - 0100
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, 1880
      • Local Institution - 0099
    • Capital Federal, Buenos Aires, Argentina, 1431
      • Local Institution - 0098
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, 1181
      • Local Institution - 0139
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Local Institution - 0095
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Local Institution - 0096
• Australia
  • Murdoch, Australia, 6150
    • Local Institution - 0074
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Local Institution - 0073
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0070
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Local Institution - 0076
    • Southport, Queensland, Australia, 4215
      • Local Institution - 0075
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Local Institution - 0140
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Local Institution - 0072
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 0071
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution - 0104
• Austria
  • Linz, Austria, 4020
    • Local Institution - 0108
  • Vienna, Austria, 1090
    • Local Institution - 0109
  • Wels, Austria, 4600
    • Local Institution - 0107
• Belgium
  • Ghent, Belgium, 9000
    • Local Institution - 0020
  • Leuven, Belgium, 3000
    • Local Institution - 0019
• Brazil
  • Rio de Janeiro, Brazil, 20793-080
    • Local Institution - 0157
  • São Paulo, Brazil, 01406-100
    • Local Institution - 0155
  • São Paulo, Brazil, 01509-010
    • Local Institution - 0156
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-090
      • Local Institution - 0152
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Local Institution - 0150
    • Porto Alegre, Rio Grande do Sul, Brazil, 91610-000
      • Local Institution - 0151
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01321-001
      • Local Institution - 0153
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Local Institution - 0149
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0133
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Local Institution - 0182
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Local Institution - 0128
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Local Institution - 0131
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Local Institution - 0172
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0148
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution - 0132
• Chile
  • Viña del Mar, Chile, 254 0364
    • Local Institution - 0103
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 8420383
      • Local Institution - 0101
    • Santiago, Santiago Metropolitan, Chile
      • Local Institution - 0102
    • Santiago, Santiago Metropolitan, Chile
      • Local Institution - 0144
• Colombia
  • Bogotá, Colombia
    • Local Institution - 0080
  • Medellín, Colombia
    • Local Institution - 0162
  • Medellín, Colombia, MEDELLIN
    • Local Institution - 0081
• Czechia
  • Brno, Czechia, 656 53
    • Local Institution - 0053
  • Hradec Králové, Czechia, 500 05
    • Local Institution - 0051
  • Olomouc, Czechia, 779 00
    • Local Institution - 0052
  • Liberec Region
    • Liberec, Liberec Region, Czechia, 460 63
      • Local Institution - 0050
• Denmark
  • Herlev, Denmark, 2730
    • Local Institution - 0158
  • Odense, Denmark, 5000
    • Local Institution - 0137
  • Central Jutland
    • Aarhus N, Central Jutland, Denmark, 8200
      • Local Institution - 0136
• Finland
  • Tampere, Finland, 33521
    • Local Institution - 0028
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00290
      • Local Institution - 0027
• France
  • Besançon, France, 25030
    • Local Institution - 0170
  • Bordeaux, France, 33075
    • Local Institution - 0062
  • La Roche-sur-Yon, France, 85925
    • Local Institution - 0169
  • Marseille, France, 13273
    • Local Institution - 0060
  • Saint-Herblain, France, 44805
    • Local Institution - 0063
  • Strasbourg, France, 67091
    • Local Institution - 0065
  • Toulouse, France, 31059
    • Local Institution - 0059
  • Villejuif, France, 94805
    • Local Institution - 0058
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75015
      • Local Institution - 0061
• Germany
  • Aachen, Germany, 52074
    • Local Institution - 0125
  • Erlangen, Germany, 91054
    • Local Institution - 0126
  • Frankfurt, Germany, 60590
    • Local Institution - 0141
  • Hamburg, Germany, 20246
    • Local Institution - 0147
  • Hanover, Germany, 30625
    • Local Institution - 0142
  • Heidelberg, Germany, 69126
    • Local Institution - 0123
  • Homburg, Germany, 66424
    • Local Institution - 0127
  • Jena, Germany, 07747
    • Local Institution - 0129
  • Magdeburg, Germany, 39120
    • Local Institution - 0143
  • München, Germany, 81675
    • Local Institution - 0124
  • Münster, Germany, 48149
    • Local Institution - 0146
  • Ulm, Germany, 89075
    • Local Institution - 0130
• Hungary
  • Budapest, Hungary, 1122
    • Local Institution - 0083
  • Debrecen, Hungary, 4032
    • Local Institution - 0082
  • Pécs, Hungary, 7624
    • Local Institution - 0084
  • Bekes County
    • Gyula, Bekes County, Hungary, 5700
      • Local Institution - 0184
• Ireland
  • Dublin, Ireland, 24
    • Local Institution - 0016
  • CORK
    • Wilton, CORK, Ireland
      • Local Institution - 0015
  • Dublin
    • Dublin, Dublin, Ireland
      • Local Institution - 0017
    • Dublin, Dublin, Ireland
      • Local Institution - 0018
• Israel
  • Haifa, Israel, 31096
    • Local Institution - 0120
  • Kfar Saba, Israel, 44281
    • Local Institution - 0117
  • Petah Tikva, Israel, 49100
    • Local Institution - 0121
  • Ramat Gan, Israel, 52621
    • Local Institution - 0118
  • Ẕerifin, Israel, 70300
    • Local Institution - 0119
• Italy
  • Arezzo, Italy, 52100
    • Local Institution - 0022
  • Meldola (fc), Italy, 47014
    • Local Institution - 0024
  • Milan, Italy, 20133
    • Local Institution - 0023
  • Naples, Italy, 80131
    • Local Institution - 0064
  • Padova, Italy, 35128
    • Local Institution - 0079
  • Pavia, Italy, 27100
    • Local Institution - 0025
  • Roma, Italy, 00149
    • Local Institution - 0026
• Japan
  • Tokyo, Japan, 113-8519
    • Local Institution - 0198
  • Yamagata, Japan, 9909585
    • Local Institution - 0203
  • Akita
    • Akita, Akita, Japan, 010-8542
      • Local Institution - 0192
  • Aomori
    • Hirosaki, Aomori, Japan, 036-8563
      • Local Institution - 0209
  • Chiba
    • Chiba, Chiba, Japan, 260-8717
      • Local Institution - 0187
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 8128582
      • Local Institution - 0196
  • Hokai-do
    • Sapporo, Hokai-do, Japan, 060-8543
      • Local Institution - 0188
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Local Institution - 0183
  • Hyōgo
    • Kobe, Hyōgo, Japan, 6500017
      • Local Institution - 0206
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 3058576
      • Local Institution - 0205
  • Iwate
    • Morioka, Iwate, Japan, 0208505
      • Local Institution - 0200
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2360004
      • Local Institution - 0186
  • Kumamoto
    • Kumamoto, Kumamoto, Japan, 8608556
      • Local Institution - 0189
  • Kyoto
    • Kyoto, Kyoto, Japan, 6028566
      • Local Institution - 0191
  • Niigata
    • Niigata, Niigata, Japan, 9518520
      • Local Institution - 0199
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 7008558
      • Local Institution - 0204
  • Osaka
    • Osakasayamashi, Osaka, Japan, 5898511
      • Local Institution - 0190
    • Suita-shi, Osaka, Japan, 565-0871
      • Local Institution - 0201
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 4313192
      • Local Institution - 0208
  • Tokushima
    • Tokushima, Tokushima, Japan, 770-8503
      • Local Institution - 0194
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Local Institution - 0202
    • Bunkyo-ku, Tokyo, Japan, 1138431
      • Local Institution - 0197
    • Bunkyo-ku, Tokyo, Japan, 1138655
      • Local Institution - 0195
    • Koto-ku, Tokyo, Japan, 1358550
      • Local Institution - 0207
    • Shinjuku-Ku, Tokyo, Japan, 1608582
      • Local Institution - 0185
    • Shinjuku-ku, Tokyo, Japan, 1628666
      • Local Institution - 0193
• Mexico
  • Oaxaca City, Mexico, 68000
    • Local Institution - 0167
  • Mexico City
    • Mexico City, Mexico City, Mexico, 14050
      • Local Institution - 0168
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Local Institution - 0171
  • Querétaro
    • Querétaro City, Querétaro, Mexico, 76090
      • Local Institution - 0175
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Local Institution - 0040
  • Nijmegen, Netherlands, 6525 GA
    • Local Institution - 0030
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1066 CX
      • Local Institution - 0029
• Poland
  • Krakow, Poland, 31-115
    • Local Institution - 0093
  • Poznan, Poland, 60-569
    • Local Institution - 0112
  • Wroclaw, Poland, 50-556
    • Local Institution - 0106
• South Korea
  • Seoul, South Korea, 120-752
    • Local Institution - 0176
  • Seoul, South Korea, 03080
    • Local Institution - 0178
  • Seoul, South Korea, 05505
    • Local Institution - 0177
• Spain
  • Barcelona, Spain, 08025
    • Local Institution - 0089
  • Barcelona, Spain, 08035
    • Local Institution - 0088
  • Madrid, Spain, 28034
    • Local Institution - 0086
  • Madrid, Spain, 28040
    • Local Institution - 0085
  • Madrid, Spain, 28041
    • Local Institution - 0087
  • Oviedo, Spain, 33011
    • Local Institution - 0111
  • Seville, Spain, 41013
    • Local Institution - 0090
• Sweden
  • Stockholm, Sweden, 171 76
    • Local Institution - 0134
• Taiwan
  • Taipei, Taiwan, 100
    • Local Institution - 0179
  • Taipei, Taiwan, 112
    • Local Institution - 0180
  • Taoyuan, Taiwan, 333
    • Local Institution - 0181
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Local Institution - 0115
  • Antalya, Turkey (Türkiye), 07070
    • Local Institution - 0114
  • Istanbul, Turkey (Türkiye), 34890
    • Local Institution - 0122
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Local Institution - 0077
  • Manchester, United Kingdom, M20 4BX
    • Local Institution - 0021
  • Northwood, United Kingdom, HA6 2RN
    • Local Institution - 0011
  • Swansea, United Kingdom, SA2 8QA
    • Local Institution - 0012
  • Greater London
    • London, Greater London, United Kingdom, SW3 6JJ
      • Local Institution - 0010
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G12 0YN
      • Local Institution - 0009
• United States
  • California
    • Duarte, California, United States, 91010
      • Local Institution - 0006
    • La Jolla, California, United States, 92093-0698
      • Local Institution - 0057
    • Los Angeles, California, United States, 90033
      • Local Institution - 0044
    • Los Angeles, California, United States, 90048
      • Local Institution - 0035
    • Stanford, California, United States, 94305
      • Local Institution - 0067
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 0138
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Local Institution - 0034
  • Florida
    • Tampa, Florida, United States, 33612
      • Local Institution - 0049
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 0068
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Local Institution - 0038
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Local Institution - 0042
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Local Institution - 0163
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Local Institution - 0048
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0004
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Local Institution - 0135
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0110
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0161
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0173
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 0046
    • Detroit, Michigan, United States, 48201
      • Local Institution - 0043
  • New York
    • Buffalo, New York, United States, 14263
      • Local Institution - 0036
    • New York, New York, United States, 10065
      • Local Institution - 0001
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0008
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0045
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 0007
    • Columbus, Ohio, United States, 43210
      • Local Institution - 0164
  • Oregon
    • Portland, Oregon, United States, 97239
      • Local Institution - 0039
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • Local Institution - 0054
    • Philadelphia, Pennsylvania, United States, 19111
      • Local Institution - 0005
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0031
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Local Institution - 0055
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Local Institution - 0159
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0066
  • Texas
    • Dallas, Texas, United States, 75246
      • Local Institution - 0056
    • Dallas, Texas, United States, 75390-8852
      • Local Institution - 0032
    • Houston, Texas, United States, 77030-4009
      • Local Institution - 0003
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 0041

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Histological confirmation of renal cell carcinoma (RCC) with a clear-cell component
• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC

• No prior systemic therapy for RCC with the following exception:

  1. One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy

     • Karnofsky Performance Status (KPS) of at least 70%
     • Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
     • Tumor tissue [formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition] must be received by the central vendor (block or unstained slides) in order to randomize a subject to study treatment. (Note: Fine Needle Aspiration [FNA] and bone metastases samples are not acceptable for submission)

Exclusion Criteria:

• Any history of or current central nervous system (CNS) metastases. Baseline imaging of the brain is required within 28 days prior to randomization
• Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, Sunitinib, Pazopanib, Axitinib, Tivozanib, and Bevacizumab)
• Prior treatment with an anti-programmed death (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (>10 mg daily Prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
• Any condition requiring systemic treatment with corticosteroids (>10 mg daily Prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses >10 mg daily Prednisone equivalents are permitted in the absence of active autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg; Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions 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; Opdivo; Biological: Ipilimumab; Other Names: Yervoy
Active Comparator: Arm B: Sunitinib 50 mg; Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks	Biological: Nivolumab; Other Names: BMS-936558; Opdivo; Drug: Sunitinib; Other Names: Sutent; Biological: Ipilimumab; Other Names: Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)	OS was defined as the time from randomization to the date of death from any cause. Survival time was censored at the date of last contact ("last known alive date") for subjects who were alive.	From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months)
Progression-Free Survival (PFS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)	PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the IRRC (as per RECIST 1.1 criteria), or death due to any cause, whichever occurred first. Subsequent therapy included anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. Subjects who died without a reported progression were considered to have progressed on the date of their death.	From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months)
Objective Response Rate (ORR) in Intermediate/Poor Risk Participants Per Independent Radiology Review Committee (IRRC) Using RECIST v1.1	ORR was defined as the proportion of randomized subjects who achieved a best response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria based on Independent Radiology Review Committee (IRRC) assessment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Objective Response Rate(ORR) in Any Risk Participants Per IRRC Using RECIST v1.1	ORR was defined as the proportion of randomized subjects who achieved a best response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria based on IRRC assessment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	From the date of randomization until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to approximately 125 months and 6 days)
Overall Survival (OS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)	Overall survival is defined as the time from randomization to the date of death from any cause. For subjects that are alive, their survival time will be censored at the date of last contact ("last known alive date"). Overall survival will be censored for subjects at the date of randomization if they were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after subject's off-treatment date.	From the date of randomization to the date of death (assessed up to approximately 125 months and 6 days)
Progression-Free Survival (PFS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)	PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the IRRC (as per RECIST 1.1 criteria), or death due to any cause, whichever occurred first. Subsequent therapy included anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. Subjects who died without a reported progression were considered to have progressed on the date of their death.	From the date of randomization to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to approximately 125 months and 6 days)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co., Ltd.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Labriola MK, George DJ. Setting a new standard for long-term survival in metastatic kidney cancer. Cancer. 2022 Jun 1;128(11):2058-2060. doi: 10.1002/cncr.34177. Epub 2022 Apr 5. No abstract available.
• Motzer RJ, McDermott DF, Escudier B, Burotto M, Choueiri TK, Hammers HJ, Barthelemy P, Plimack ER, Porta C, George S, Powles T, Donskov F, Gurney H, Kollmannsberger CK, Grimm MO, Barrios C, Tomita Y, Castellano D, Grunwald V, Rini BI, McHenry MB, Lee CW, McCarthy J, Ejzykowicz F, Tannir NM. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer. 2022 Jun 1;128(11):2085-2097. doi: 10.1002/cncr.34180. Epub 2022 Apr 5.
• Albiges L, Tannir NM, Burotto M, McDermott D, Plimack ER, Barthelemy P, Porta C, Powles T, Donskov F, George S, Kollmannsberger CK, Gurney H, Grimm MO, Tomita Y, Castellano D, Rini BI, Choueiri TK, Leung D, Saggi SS, Lee CW, McHenry MB, Motzer RJ. First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial. Eur Urol. 2022 Mar;81(3):266-271. doi: 10.1016/j.eururo.2021.10.001. Epub 2021 Nov 5.
• Albiges L, Tannir NM, Burotto M, McDermott D, Plimack ER, Barthelemy P, Porta C, Powles T, Donskov F, George S, Kollmannsberger CK, Gurney H, Grimm MO, Tomita Y, Castellano D, Rini BI, Choueiri TK, Saggi SS, McHenry MB, Motzer RJ. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020 Nov;5(6):e001079. doi: 10.1136/esmoopen-2020-001079.
• 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.
• Tomita Y, Kondo T, Kimura G, Inoue T, Wakumoto Y, Yao M, Sugiyama T, Oya M, Fujii Y, Obara W, Motzer RJ, Uemura H. Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma: analysis of Japanese patients in CheckMate 214 with extended follow-up. Jpn J Clin Oncol. 2020 Jan 24;50(1):12-19. doi: 10.1093/jjco/hyz132.
• Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.
• Motzer RJ, Escudier B, McDermott DF, Aren Frontera O, Melichar B, Powles T, Donskov F, Plimack ER, Barthelemy P, Hammers HJ, George S, Grunwald V, Porta C, Neiman V, Ravaud A, Choueiri TK, Rini BI, Salman P, Kollmannsberger CK, Tykodi SS, Grimm MO, Gurney H, Leibowitz-Amit R, Geertsen PF, Amin A, Tomita Y, McHenry MB, Saggi SS, Tannir NM. Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial. J Immunother Cancer. 2020 Jul;8(2):e000891. doi: 10.1136/jitc-2020-000891.
• Motzer RJ, Rini BI, McDermott DF, Aren Frontera O, Hammers HJ, Carducci MA, Salman P, Escudier B, Beuselinck B, Amin A, Porta C, George S, Neiman V, Bracarda S, Tykodi SS, Barthelemy P, Leibowitz-Amit R, Plimack ER, Oosting SF, Redman B, Melichar B, Powles T, Nathan P, Oudard S, Pook D, Choueiri TK, Donskov F, Grimm MO, Gurney H, Heng DYC, Kollmannsberger CK, Harrison MR, Tomita Y, Duran I, Grunwald V, McHenry MB, Mekan S, Tannir NM; CheckMate 214 investigators. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019 Oct;20(10):1370-1385. doi: 10.1016/S1470-2045(19)30413-9. Epub 2019 Aug 16.
• Cella D, Grunwald V, Escudier B, Hammers HJ, George S, Nathan P, Grimm MO, Rini BI, Doan J, Ivanescu C, Paty J, Mekan S, Motzer RJ. Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial. Lancet Oncol. 2019 Feb;20(2):297-310. doi: 10.1016/S1470-2045(18)30778-2. Epub 2019 Jan 15.
• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.
• Mantia CM, Jegede OA, Plimack ER, Powles T, Motzer RJ, Tannir NM, Lee CH, Tomita Y, Voss MH, Choueiri TK, Rini BI, Hammers HJ, Escudier B, Albiges L, Rosenblatt L, Atkins MB, Regan MM, McDermott DF. Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214. J Immunother Cancer. 2024 Jul 25;12(7):e009495. doi: 10.1136/jitc-2024-009495.
• Cella D, Choueiri TK, Hamilton M, Blum SI, Ivanescu C, Karu K, Ejzykowicz F, Motzer RJ. The Relationship Between Health-Related Quality of Life and Overall Survival in Patients With Advanced Renal Cell Carcinoma in CheckMate 214. Oncologist. 2024 Jun 3;29(6):511-518. doi: 10.1093/oncolo/oyae003.
• Rini BI, Signoretti S, Choueiri TK, McDermott DF, Motzer RJ, George S, Powles T, Donskov F, Tykodi SS, Pal SK, Gupta S, Lee CW, Jiang R, Tannir NM. Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma. J Immunother Cancer. 2022 Dec;10(12):e005445. doi: 10.1136/jitc-2022-005445.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2014
• Primary Completion (Actual): June 26, 2017
• Study Completion (Actual): March 21, 2025

Study Registration Dates

• First Submitted: September 1, 2014
• First Submitted That Met QC Criteria: September 3, 2014
• First Posted (Estimated): September 4, 2014

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Indoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pyrroles; Sunitinib; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA209-214; 2014-001750-42 (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