Renal Cell CarcinomaPhase 3CheckMate 9ERNCT03141177
A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
A Phase 3 study testing Nivolumab, Cabozantinib and Sunitinib in people with Renal Cell Carcinoma, run by Bristol-Myers Squibb at 135 sites in 18 countries.
Trial summary
The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in previously untreated advanced or metastatic renal cell carcinoma Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Nivolumab, Cabozantinib and Sunitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 701 participants
- Where
- 135 sitesin 18 countries
- Study dates
- 23 Jul 2017to 1 Apr 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological confirmation of RCC with a clear-cell component, including participants who may also have sarcomatoid features
- 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:
- One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets VEGF or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
Who cannot join
- Any active CNS metastases
- Any active, known or suspected autoimmune disease
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
- Participants who have received a live/attenuated vaccine within 30 days of first treatment
- Other protocol defined inclusion/exclusion criteria could apply
Trial locations and contacts
135 sites in 18 countries.
135 sites in 18 countries
United States30 sites
Local Institution - 0135
Allentown, Pennsylvania, 18103
Local Institution - 0127
Athens, Georgia, 30607
Local Institution - 0103
Aurora, Colorado, 80045
Local Institution - 0080
Austin, Texas, 78705
Local Institution - 0133
Bakersfield, California, 93309
Local Institution - 0113
Boston, Massachusetts, 02114
Local Institution - 0037
Boston, Massachusetts, 02215
Local Institution - 0040
Buffalo, New York, 14263
Local Institution - 0036
Chicago, Illinois, 60612
Local Institution - 0075
Dallas, Texas, 75246
Local Institution - 0077
Daphne, Alabama, 36526
Local Institution - 0091
Fort Wayne, Indiana, 46804
Local Institution - 0044
Goodyear, Arizona, 85338
Local Institution - 0068
Houston, Texas, 77030
Local Institution - 0106
Kansas City, Missouri, 64132
Local Institution - 0102
Las Vegas, Nevada, 89169
Local Institution - 0093
Los Angeles, California, 90404
Local Institution - 0105
Nashville, Tennessee, 37203
Local Institution - 0017
New York, New York, 10065
Local Institution - 0086
Newnan, Georgia, 30265
Local Institution - 0131
Norfolk, Virginia, 23502
Local Institution - 0067
Portland, Oregon, 97239
Local Institution - 0090
Redondo Beach, California, 90277
Local Institution - 0088
San Luis Obispo, California, 93401
Central Coast Medical Oncology Corporation
Santa Maria, California, 93454
Local Institution - 0078
Sherman, Texas, 75090
Local Institution - 0035
St Louis, Missouri, 63110
Local Institution - 0132
Tucson, Arizona, 85724-5024
Local Institution - 0087
Wichita, Kansas, 67214
Local Institution - 0042
Zion, Illinois, 60099
Japan25 sites
Local Institution - 0152
Adachi-ku, Tokyo, 123-8558
Local Institution - 0148
Akita, Akita, 010-8543
Local Institution - 0158
Bunkyo-ku, Tokyo, 1138519
Local Institution - 0151
Bunkyo-ku, Tokyo, 1138603
Local Institution - 0167
Chiba, 260-8717
Local Institution - 0161
Fukuoka, 812-8582
Local Institution - 0155
Hidaka-shi, Saitama, 3501298
Local Institution - 0156
Hirosaki, Aomori, 036-8563
Local Institution - 0168
Kobe, Hyōgo, 6500017
Local Institution - 0173
Minato-ku, Tokyo, 105-8470
Local Institution - 0159
Morioka, Iwate, 0208505
Local Institution - 0162
Nagasaki, 8528501
Local Institution - 0150
Niigata, Niigata, 9518520
Local Institution - 0169
Okayama, Okayama-ken, 7008558
Local Institution - 0170
Osaka, Osaka, 5418567
Local Institution - 0154
Osaka, Osaka-shi, 545-8586
Local Institution - 0160
Osakasayamashi, Osaka, 5898511
Local Institution - 0164
Sapporo, Hokkaido, 0608543
Local Institution - 0157
Sapporo, Hokkaido, 0608648
Local Institution - 0163
Suita-shi, Osaka, 565-0871
Local Institution - 0153
Tokushima, Tokushima, 7708503
Local Institution - 0149
Tokyo, 160-8582
Local Institution - 0165
Yamagata, 9909585
Local Institution - 0171
Yokohama, Kanagawa, 236-0004
Local Institution - 0166
Yokohama, Kanagawa, 241-8515
Australia10 sites
Local Institution - 0007
Doubleview, Western Australia, 6018
Local Institution - 0004
Elizabeth Vale, South Australia, 5112
Local Institution - 0006
Herston, Queensland, 4006
Local Institution - 0005
Malvern, Victoria, 3144
Local Institution - 0002
North Ryde, New South Wales, 0
Local Institution - 0129
South Brisbane, 4101
Local Institution - 0001
Southport, Queensland, 4215
Local Institution - 0008
Sydney, New South Wales, 2010
Local Institution - 0009
Sydney, New South Wales, 2139
Local Institution - 0073
Westmead, New South Wales, 2145
Mexico9 sites
Local Institution - 0136
Mérida, Yucatán, 97125
Local Institution - 0062
Mexico City, Mexico City, 06100
Local Institution - 0116
Mexico City, Mexico City, 14080
Local Institution - 0065
Monterrey, Nuevo León, 64000
Local Institution - 0143
Monterrey, Nuevo León, 64060
Local Institution - 0064
Monterrey, Nuevo León, 64460
Local Institution - 0063
Querétaro City, Querétaro, 76000
Local Institution - 0115
Tlalpan, Mexico City, 14080
Local Institution - 0108
Zapopan, Jalisco, 45070
Brazil8 sites
Local Institution - 0058
Barretos, São Paulo, 14784-400
Local Institution - 0057
Belo Horizonte, Minas Gerais, 30130-090
Local Institution - 0119
Ijuí, Rio Grande do Sul, 98700-000
Local Institution - 0056
Porto Alegre, Rio Grande do Sul, 90610-000
Local Institution - 0060
Porto Alegre, Rio Grande do Sul, 91350-200
Local Institution - 0066
Rio de Janeiro, 20231-050
Local Institution - 0074
São Paulo, 01323-020
Local Institution - 0061
São Paulo, 05651901
Argentina7 sites
Local Institution - 0046
CABA, Buenos Aires, C1120AAT
Local Institution - 0138
CABA, 1426
Local Institution - 0048
Ciudad Autonoma de Buenos Aire, Buenos Aires, 1181
Local Institution - 0050
Córdoba, 5000
Local Institution - 0049
Córdoba, X5004FHP
Local Institution - 0047
San Miguel de Tucumán, 4000
Local Institution - 0114
Viedma, Río Negro Province, 8500
Germany7 sites
Local Institution - 0013
Aachen, 52074
Local Institution - 0016
Bonn, 53127
Local Institution - 0117
Essen, 45136
Local Institution - 0023
Jena, 07747
Local Institution - 0010
München, 81675
Local Institution - 0014
Nuremberg, 90419
Local Institution - 0011
Tübingen, 72076
Italy7 sites
Local Institution - 0054
Arezzo, 52100
Local Institution - 0052
Milan, 20132
Local Institution - 0055
Naples, 80131
Local Institution - 0053
Padova, Padova
Local Institution - 0051
Pavia, 27100
Local Institution - 0147
Pavia, 27100
Local Institution - 0172
Terni, 05100
Turkey (Türkiye)7 sites
Local Institution - 0107
Ankara, 06018
Local Institution - 0139
Ankara, 06620
Local Institution - 0094
Ankara, 06800
Local Institution - 0096
Antalya, 07070
Local Institution - 0097
Denizli, 20070
Local Institution - 0095
Edirne, 22030
Local Institution - 0146
Istanbul, 34300
Spain6 sites
Local Institution - 0125
Barcelona, 08035
Local Institution - 0121
Madrid, 28009
Local Institution - 0120
Madrid, 28041
Local Institution - 0144
Santander, 39008
Local Institution - 0124
Seville, 41013
Local Institution - 0123
Valencia, 46014
Israel4 sites
Local Institution - 0072
Haifa, 3109601
Local Institution - 0070
Kfar Saba, 44281
Local Institution - 0071
Petah Tikva, 49414
Local Institution - 0069
Ramat Gan, 52621
Poland3 sites
Local Institution - 0084
Biała Podlaska, 21-500
Local Institution - 0130
Bydgoszcz, 85796
Local Institution - 0085
Gdansk, 80-219
United Kingdom3 sites
Local Institution - 0111
London, EC1A 7BE
Local Institution - 0109
Manchester, M20 4BX
Local Institution - 0140
Truro, TR1 3LJ
Czechia2 sites
Local Institution - 0034
Hradec Králové, 500 05
Local Institution - 0033
Olomouc, 779 00
Greece2 sites
Local Institution - 0082
Athens, 115 28
Local Institution - 0083
Thessaloniki, 546 45
Romania2 sites
Local Institution - 0021
Cluj-Napoca, 400015
Local Institution - 0022
Craiova, 200542
Russia2 sites
Local Institution - 0020
Moscow, 125284
Local Institution - 0099
Saint Petersburg, 197758
About this study
Official title: A Phase 3, Randomized, Open-Label Study of Nivolumab Combined With Cabozantinib Versus Sunitinib in Participants With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in previously untreated advanced or metastatic renal cell carcinoma
- Conditions
- Renal Cell Carcinoma
- Being tested
- Nivolumab, Cabozantinib, Sunitinib, Ipilimumab
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
Also called Opdivo, BMS-936558
Specified dose on specified day
CabozantinibDrug
Also called Cabometyx
Specified dose on specified days
SunitinibDrug
Also called Sutent
Specified dose on specified days.
IpilimumabBiological
Also called Yervoy, BMS-734016
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Doublet | Experimental | Nivolumab and Cabozantinib Receives: Biological: Nivolumab; Drug: Cabozantinib |
| Monotherapy | Active comparator | Sunitinib Receives: Drug: Sunitinib |
| Triplet | Experimental | Nivolumab, Ipilimumab, Cabozantinib
*Enrollment to the triplet arm was discontinued by protocol amendment Receives: Biological: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS is defined as the time from date of randomization to the first documented tumor progression date or death due to any cause, whichever occurs first based on BICR assessment using RECIST v1.1. Participants who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment on or prior to initiation of subsequent anti-cancer therapy. Progressive disease (PD); 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study
Measured: From randomization date to date of first documented tumor progression or death, whichever occurs first (Up to 31 months)
Secondary outcomes (8)
Overall Survival (OS)
Overall Survival is defined as the time between the date of randomization and the date of death due to any cause. For participants that are alive, their survival time will be censored at the date of last contact date (or "last known alive date").
Measured: From randomization date to death date (Up to 31 months)
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the percentage of randomized participants who achieve a best response of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1 criteria) divided by the number of all randomized participants.
Complete response (CR): Disappearance of all target lesions. Partial response (PR): 30% decrease in the sum of diameters of target lesions.
Measured: Up to 31 Months
Number of Participants Experiencing Adverse Events (AEs)
Number of participants experiencing various types of any grade adverse events (AEs) during the specified time frame.
Measured: From first dose to 100 days following last dose (Up to 32 Months)
Number of Participants Experiencing Serious Adverse Events (SAEs)
Number of participants experiencing various types of any grade serious adverse events (SAEs) during the specified time frame.
Measured: From first to dose to 100 days following last dose (Up to 32 months)
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Number of participants experiencing various types of any grade adverse events (AEs) leading to discontinuation during the specified time frame.
Measured: From first dose to 30 days following last dose (Up to 30 months)
Number of Deaths
Number of deaths due to any cause during the specified time frame.
Measured: From first dose to (up to 31 months) following first dose
Number of Participants With Laboratory Abnormalities
Number of participants experiencing laboratory abnormalities in hematology, serum chemistry and electrolytes with grade 3 or higher during the specified time frame.
Measured: From first dose to 30 days following last dose (Up to 30 Months)
Number of Participants With Laboratory Values Grade Shifting From Baseline
Number of participants experiencing worsening shift from baseline in any grade and grade 3-4 of laboratory values during the specified time frame.
Measured: From first dose to 30 days following last dose (Up to 30 Months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2017
- Study start23 Jul 2017
- Primary completion12 Feb 2020
- Study completion1 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 701 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Exelixis, Ono Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03141177
- Sponsor's protocol ID
- CA209-9ER
- Other IDs
- 2017-000759-20, 2017
- Acronym
- CheckMate 9ER
- Status last verified
- Jul 2026
- First submitted
- 3 May 2017
- Last updated
- 24 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cella D, Derosa M, Floden L, Giles RH, Lothgren M, Ogareva A, Powles T, Purnajo I, Choueiri TK, Bergerot C, Motzer RJ, Bedke J. Summary of Research: Health-Related Quality-of-Life Profile and Clinical Outcomes in First-Line Advanced Renal Cell Carcinoma: A Modeling Analysis Based on the CheckMate 9ER Study. Adv Ther. 2026 Oct 8. doi: 10.1007/s12325-026-03780-4. Online ahead of print.
PubMed 42848188Grimm MO, Karim E, Kapetanakis V, Lothgren M, Ogareva A, Shukla P, Truscott J, Porta C. Summary of Research: Two-Stage Estimation of Overall Survival in the Phase 3 CheckMate 9ER Trial, Adjusting for the Impact of Subsequent Therapy. Adv Ther. 2026 Oct 8. doi: 10.1007/s12325-026-03773-3. Online ahead of print.
PubMed 42848187Bergerot C, Yu S, Yang M, Martins B, Du M, Perez Torrealba J, Hall T, Samant N, Motzer RJ, Cella D. Identification of key symptoms impacting HRQOL in advanced renal cell carcinoma: nivolumab plus cabozantinib versus sunitinib in CheckMate 9ER. Oncologist. 2026 Aug 14:oyag329. doi: 10.1093/oncolo/oyag329. Online ahead of print.
PubMed 42605077Viray H, M Mantia C, Jegede OA, Atkins MB, Rosenblatt L, Choueiri TK, McDermott DF, Regan MM. Partitioned overall survival: comprehensive analysis of survival states over 4 years in CheckMate 9ER comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma. J Immunother Cancer. 2026 Jan 30;14(1):e013546. doi: 10.1136/jitc-2025-013546.
PubMed 41617395Grimm MO, Karim E, Kapetanakis V, Lothgren M, Ogareva A, Shukla P, Truscott J, Porta C. Two-Stage Estimation of Overall Survival in the Phase 3 CheckMate 9ER Trial, Adjusting for the Impact of Subsequent Therapy. Oncol Ther. 2026 Mar;14(1):253-268. doi: 10.1007/s40487-025-00393-9. Epub 2025 Nov 15.
PubMed 41239083Motzer RJ, Escudier B, Burotto M, Powles T, Apolo AB, Bourlon MT, Shah AY, Porta C, Suarez C, Barrios CH, Richardet M, Gurney H, Kessler ER, Tomita Y, Bedke J, Scheffold C, Askelson M, Panzica J, Zhang J, van Kooten Losio M, Choueiri TK. Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial. Ann Oncol. 2026 Jan;37(1):33-43. doi: 10.1016/j.annonc.2025.09.006. Epub 2025 Sep 23.
PubMed 40998092Cella D, Motzer RJ, Suarez C, Blum SI, Ejzykowicz F, Hamilton M, Wallace JF, Simsek B, Zhang J, Ivanescu C, Choueiri TK, Apolo AB. Plain language summary of quality of life in CheckMate 9ER: Cabozantinib plus nivolumab in advanced renal cell carcinoma. Future Oncol. 2025 Jan;21(2):181-194. doi: 10.1080/14796694.2024.2415786. Epub 2024 Oct 25.
PubMed 39452894Powles T, Burotto M, Escudier B, Apolo AB, Bourlon MT, Shah AY, Suarez C, Porta C, Barrios CH, Richardet M, Gurney H, Kessler ER, Tomita Y, Bedke J, George S, Scheffold C, Wang P, Fedorov V, Motzer RJ, Choueiri TK. Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial. ESMO Open. 2024 May;9(5):102994. doi: 10.1016/j.esmoop.2024.102994. Epub 2024 Apr 20.
PubMed 38642472Petersohn S, McGregor B, Klijn SL, May JR, Ejzykowicz F, Kurt M, Dyer M, Malcolm B, Branchoux S, Nickel K, George S, Kroep S. Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma. J Comp Eff Res. 2023 Aug;12(8):e230004. doi: 10.57264/cer-2023-0004. Epub 2023 Jul 11.
PubMed 37431849Aldin 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.
PubMed 37146227Tran BD, Li J, Ly N, Faggioni R, Roskos L. Cabozantinib exposure-response analysis for the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib in first-line advanced renal cell carcinoma. Cancer Chemother Pharmacol. 2023 Feb;91(2):179-189. doi: 10.1007/s00280-022-04500-9. Epub 2023 Jan 10.
PubMed 36625894Apolo AB, Powles T, Escudier B, Burotto M, Zhang J, Simsek B, Scheffold C, Motzer RJ, Choueiri TK. Nivolumab plus ipilimumab plus cabozantinib triplet combination for patients with previously untreated advanced renal cell carcinoma: Results from a discontinued arm of the phase III CheckMate 9ER trial. Eur J Cancer. 2022 Dec;177:63-71. doi: 10.1016/j.ejca.2022.09.020. Epub 2022 Oct 4.
PubMed 36327527Motzer RJ, Powles T, Burotto M, Escudier B, Bourlon MT, Shah AY, Suarez C, Hamzaj A, Porta C, Hocking CM, Kessler ER, Gurney H, Tomita Y, Bedke J, Zhang J, Simsek B, Scheffold C, Apolo AB, Choueiri TK. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Jul;23(7):888-898. doi: 10.1016/S1470-2045(22)00290-X. Epub 2022 Jun 7.
PubMed 35688173Cella D, Motzer RJ, Suarez C, Blum SI, Ejzykowicz F, Hamilton M, Wallace JF, Simsek B, Zhang J, Ivanescu C, Apolo AB, Choueiri TK. Patient-reported outcomes with first-line nivolumab plus cabozantinib versus sunitinib in patients with advanced renal cell carcinoma treated in CheckMate 9ER: an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):292-303. doi: 10.1016/S1470-2045(21)00693-8. Epub 2022 Jan 12.
PubMed 35032437Hamuro L, Hu Z, Passarell J, Barcomb H, Zhang J, Goldstein S, Bello A, Roy A, Zhu L. Exposure-Response Analysis to Support Nivolumab Once Every 4 Weeks Dosing in Combination with Cabozantinib in Renal Cell Carcinoma. Clin Cancer Res. 2022 Apr 14;28(8):1603-1613. doi: 10.1158/1078-0432.CCR-21-3149.
PubMed 34980597