A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

NCT03141177 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: CA209-9ER2017-000759-20
• Study Type: interventional
• Target: 701
• Locations: 18 countries
• Sites: 135

Brief 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

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  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)

  From randomization date to death date (Up to 31 months)

• Objective Response Rate (ORR)

  Up to 31 Months

• Number of Participants Experiencing Adverse Events (AEs)

  From first dose to 100 days following last dose (Up to 32 Months)

• Number of Participants Experiencing Serious Adverse Events (SAEs)

  From first to dose to 100 days following last dose (Up to 32 months)

• Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

  From first dose to 30 days following last dose (Up to 30 months)

Study Arms (3)

Doublet

EXPERIMENTAL

Nivolumab and Cabozantinib

Biological: Nivolumab; Drug: Cabozantinib

Monotherapy

ACTIVE COMPARATOR

Sunitinib

Drug: Sunitinib

Triplet

EXPERIMENTAL

Nivolumab, Ipilimumab, Cabozantinib \*Enrollment to the triplet arm was discontinued by protocol amendment

Biological: Ipilimumab

Interventions

Nivolumab BIOLOGICAL

Specified dose on specified day

Also known as: Opdivo, BMS-936558

Doublet

Cabozantinib DRUG

Specified dose on specified days

Also known as: Cabometyx

Doublet

Sunitinib DRUG

Specified dose on specified days.

Also known as: Sutent

Monotherapy

Ipilimumab BIOLOGICAL

Specified dose on specified days

Also known as: Yervoy, BMS-734016

Triplet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• i) 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Exelixis: collaborator
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (135)

Local Institution - 0077

Daphne, Alabama, 36526, United States

Location

Local Institution - 0044

Goodyear, Arizona, 85338, United States

Location

Local Institution - 0132

Tucson, Arizona, 85724-5024, United States

Location

Local Institution - 0133

Bakersfield, California, 93309, United States

Location

Local Institution - 0093

Los Angeles, California, 90404, United States

Location

Local Institution - 0090

Redondo Beach, California, 90277, United States

Location

Local Institution - 0088

San Luis Obispo, California, 93401, United States

Location

Central Coast Medical Oncology Corporation

Santa Maria, California, 93454, United States

Location

Local Institution - 0103

Aurora, Colorado, 80045, United States

Location

Local Institution - 0127

Athens, Georgia, 30607, United States

Location

Local Institution - 0086

Newnan, Georgia, 30265, United States

Location

Local Institution - 0036

Chicago, Illinois, 60612, United States

Location

Local Institution - 0042

Zion, Illinois, 60099, United States

Location

Local Institution - 0091

Fort Wayne, Indiana, 46804, United States

Location

Local Institution - 0087

Wichita, Kansas, 67214, United States

Location

Local Institution - 0113

Boston, Massachusetts, 02114, United States

Location

Local Institution - 0037

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0106

Kansas City, Missouri, 64132, United States

Location

Local Institution - 0035

St Louis, Missouri, 63110, United States

Location

Local Institution - 0102

Las Vegas, Nevada, 89169, United States

Location

Local Institution - 0040

Buffalo, New York, 14263, United States

Location

Local Institution - 0017

New York, New York, 10065, United States

Location

Local Institution - 0067

Portland, Oregon, 97239, United States

Location

Local Institution - 0135

Allentown, Pennsylvania, 18103, United States

Location

Local Institution - 0105

Nashville, Tennessee, 37203, United States

Location

Local Institution - 0080

Austin, Texas, 78705, United States

Location

Local Institution - 0075

Dallas, Texas, 75246, United States

Location

Local Institution - 0068

Houston, Texas, 77030, United States

Location

Local Institution - 0078

Sherman, Texas, 75090, United States

Location

Local Institution - 0131

Norfolk, Virginia, 23502, United States

Location

Local Institution - 0046

CABA, Buenos Aires, C1120AAT, Argentina

Location

Local Institution - 0048

Ciudad Autonoma de Buenos Aire, Buenos Aires, 1181, Argentina

Location

Local Institution - 0114

Viedma, Río Negro Province, 8500, Argentina

Location

Local Institution - 0138

CABA, 1426, Argentina

Location

Local Institution - 0050

Córdoba, 5000, Argentina

Location

Local Institution - 0049

Córdoba, X5004FHP, Argentina

Location

Local Institution - 0047

San Miguel de Tucumán, 4000, Argentina

Location

Local Institution - 0002

North Ryde, New South Wales, 0, Australia

Location

Local Institution - 0008

Sydney, New South Wales, 2010, Australia

Location

Local Institution - 0009

Sydney, New South Wales, 2139, Australia

Location

Local Institution - 0073

Westmead, New South Wales, 2145, Australia

Location

Local Institution - 0006

Herston, Queensland, 4006, Australia

Location

Local Institution - 0001

Southport, Queensland, 4215, Australia

Location

Local Institution - 0004

Elizabeth Vale, South Australia, 5112, Australia

Location

Local Institution - 0005

Malvern, Victoria, 3144, Australia

Location

Local Institution - 0007

Doubleview, Western Australia, 6018, Australia

Location

Local Institution - 0129

South Brisbane, 4101, Australia

Location

Local Institution - 0057

Belo Horizonte, Minas Gerais, 30130-090, Brazil

Location

Local Institution - 0119

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Local Institution - 0056

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Local Institution - 0060

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Local Institution - 0058

Barretos, São Paulo, 14784-400, Brazil

Location

Local Institution - 0066

Rio de Janeiro, 20231-050, Brazil

Location

Local Institution - 0074

São Paulo, 01323-020, Brazil

Location

Local Institution - 0061

São Paulo, 05651901, Brazil

Location

Local Institution - 0045

Santiago, Santiago Metropolitan, 8420383, Chile

Location

Local Institution - 0034

Hradec Králové, 500 05, Czechia

Location

Local Institution - 0033

Olomouc, 779 00, Czechia

Location

Local Institution - 0013

Aachen, 52074, Germany

Location

Local Institution - 0016

Bonn, 53127, Germany

Location

Local Institution - 0117

Essen, 45136, Germany

Location

Local Institution - 0023

Jena, 07747, Germany

Location

Local Institution - 0010

München, 81675, Germany

Location

Local Institution - 0014

Nuremberg, 90419, Germany

Location

Local Institution - 0011

Tübingen, 72076, Germany

Location

Local Institution - 0082

Athens, 115 28, Greece

Location

Local Institution - 0083

Thessaloniki, 546 45, Greece

Location

Local Institution - 0072

Haifa, 3109601, Israel

Location

Local Institution - 0070

Kfar Saba, 44281, Israel

Location

Local Institution - 0071

Petah Tikva, 49414, Israel

Location

Local Institution - 0069

Ramat Gan, 52621, Israel

Location

Local Institution - 0054

Arezzo, 52100, Italy

Location

Local Institution - 0052

Milan, 20132, Italy

Location

Local Institution - 0055

Napoli, 80131, Italy

Location

Local Institution - 0053

Padua, Padova, Italy

Location

Local Institution - 0051

Pavia, 27100, Italy

Location

Local Institution - 0147

Pavia, 27100, Italy

Location

Local Institution - 0172

Terni, 05100, Italy

Location

Local Institution - 0148

Akita, Akita, 010-8543, Japan

Location

Local Institution - 0156

Hirosaki, Aomori, 036-8563, Japan

Location

Local Institution - 0164

Sapporo, Hokkaido, 0608543, Japan

Location

Local Institution - 0157

Sapporo, Hokkaido, 0608648, Japan

Location

Local Institution - 0168

Kobe, Hyōgo, 6500017, Japan

Location

Local Institution - 0159

Morioka, Iwate, 0208505, Japan

Location

Local Institution - 0171

Yokohama, Kanagawa, 236-0004, Japan

Location

Local Institution - 0166

Yokohama, Kanagawa, 241-8515, Japan

Location

Local Institution - 0150

Niigata, Niigata, 9518520, Japan

Location

Local Institution - 0169

Okayama, Okayama-ken, 7008558, Japan

Location

Local Institution - 0170

Osaka, Osaka, 5418567, Japan

Location

Local Institution - 0160

Osakasayamashi, Osaka, 5898511, Japan

Location

Local Institution - 0163

Suita-shi, Osaka, 565-0871, Japan

Location

Local Institution - 0154

Osaka, Osaka-shi, 545-8586, Japan

Location

Local Institution - 0155

Hidaka-shi, Saitama, 3501298, Japan

Location

Local Institution - 0153

Tokushima, Tokushima, 7708503, Japan

Location

Local Institution - 0152

Adachi-ku, Tokyo, 123-8558, Japan

Location

Local Institution - 0158

Bunkyo-ku, Tokyo, 1138519, Japan

Location

Local Institution - 0151

Bunkyo-ku, Tokyo, 1138603, Japan

Location

Local Institution - 0173

Minato-ku, Tokyo, 105-8470, Japan

Location

Local Institution - 0167

Chiba, 260-8717, Japan

Location

Local Institution - 0161

Fukuoka, 812-8582, Japan

Location

Local Institution - 0162

Nagasaki, 8528501, Japan

Location

Local Institution - 0149

Tokyo, 160-8582, Japan

Location

Local Institution - 0165

Yamagata, 9909585, Japan

Location

Local Institution - 0108

Zapopan, Jalisco, 45070, Mexico

Location

Local Institution - 0062

Mexico City, Mexico City, 06100, Mexico

Location

Local Institution - 0116

Mexico City, Mexico City, 14080, Mexico

Location

Local Institution - 0115

Tlalpan, Mexico City, 14080, Mexico

Location

Local Institution - 0065

Monterrey, Nuevo León, 64000, Mexico

Location

Local Institution - 0143

Monterrey, Nuevo León, 64060, Mexico

Location

Local Institution - 0064

Monterrey, Nuevo León, 64460, Mexico

Location

Local Institution - 0063

Querétaro City, Querétaro, 76000, Mexico

Location

Local Institution - 0136

Mérida, Yucatán, 97125, Mexico

Location

Local Institution - 0084

Biała Podlaska, 21-500, Poland

Location

Local Institution - 0130

Bydgoszcz, 85796, Poland

Location

Local Institution - 0085

Gdansk, 80-219, Poland

Location

Local Institution - 0021

Cluj-Napoca, 400015, Romania

Location

Local Institution - 0022

Craiova, 200542, Romania

Location

Local Institution - 0020

Moscow, 125284, Russia

Location

Local Institution - 0099

Saint Petersburg, 197758, Russia

Location

Local Institution - 0125

Barcelona, 08035, Spain

Location

Local Institution - 0121

Madrid, 28009, Spain

Location

Local Institution - 0120

Madrid, 28041, Spain

Location

Local Institution - 0144

Santander, 39008, Spain

Location

Local Institution - 0124

Seville, 41013, Spain

Location

Local Institution - 0123

Valencia, 46014, Spain

Location

Local Institution - 0107

Ankara, 06018, Turkey (Türkiye)

Location

Local Institution - 0139

Ankara, 06620, Turkey (Türkiye)

Location

Local Institution - 0094

Ankara, 06800, Turkey (Türkiye)

Location

Local Institution - 0096

Antalya, 07070, Turkey (Türkiye)

Location

Local Institution - 0097

Denizli, 20070, Turkey (Türkiye)

Location

Local Institution - 0095

Edirne, 22030, Turkey (Türkiye)

Location

Local Institution - 0146

Istanbul, 34300, Turkey (Türkiye)

Location

Local Institution - 0111

London, EC1A 7BE, United Kingdom

Location

Local Institution - 0109

Manchester, M20 4BX, United Kingdom

Location

Local Institution - 0140

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (13)

• Viray 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.

  PMID: 41617395 DERIVED

• Grimm 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. 2025 Nov 15. doi: 10.1007/s40487-025-00393-9. Online ahead of print.

  PMID: 41239083 DERIVED

• Cella 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.

  PMID: 39452894 DERIVED

• Powles 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.

  PMID: 38642472 DERIVED

• Petersohn 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.

  PMID: 37431849 DERIVED

• 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.

  PMID: 37146227 DERIVED

• Tran 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.

  PMID: 36625894 DERIVED

• Apolo 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.

  PMID: 36327527 DERIVED

• Motzer 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.

  PMID: 35688173 DERIVED

• Cella 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.

  PMID: 35032437 DERIVED

• Hamuro 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.

  PMID: 34980597 DERIVED

• Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, Oyervides Juarez VM, Hsieh JJ, Basso U, Shah AY, Suarez C, Hamzaj A, Goh JC, Barrios C, Richardet M, Porta C, Kowalyszyn R, Feregrino JP, Zolnierek J, Pook D, Kessler ER, Tomita Y, Mizuno R, Bedke J, Zhang J, Maurer MA, Simsek B, Ejzykowicz F, Schwab GM, Apolo AB, Motzer RJ; CheckMate 9ER Investigators. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021 Mar 4;384(9):829-841. doi: 10.1056/NEJMoa2026982.

  PMID: 33657295 DERIVED

• Hofmann F, Hwang EC, Lam TB, Bex A, Yuan Y, Marconi LS, Ljungberg B. Targeted therapy for metastatic renal cell carcinoma. Cochrane Database Syst Rev. 2020 Oct 14;10(10):CD012796. doi: 10.1002/14651858.CD012796.pub2.

  PMID: 33058158 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab; cabozantinib; Sunitinib; Ipilimumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

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

Study Record Dates

• First Submitted: May 3, 2017
• First Posted: May 4, 2017
• Study Start: July 23, 2017
• Primary Completion: February 12, 2020
• Study Completion: January 16, 2026
• Last Updated: June 6, 2025
• Results First Posted: April 26, 2022

Record last verified: 2025-05

Locations

AU (10); PL (3); CZ (2); ES (6); TU (7); AR (7); IL (4); JP (25); CL (1); DE (7); ME (9); BR (8); IT (7); RU (2); RO (2); GB (3); US (30); GR (2)