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

NCT ID: NCT03141177

Last Updated: 2025-06-06

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

701 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-23

Study Completion Date

2026-01-16

Brief Summary

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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

Detailed Description

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Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Doublet

Nivolumab and Cabozantinib

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Specified dose on specified day

Cabozantinib

Intervention Type DRUG

Specified dose on specified days

Monotherapy

Sunitinib

Group Type ACTIVE_COMPARATOR

Sunitinib

Intervention Type DRUG

Specified dose on specified days.

Triplet

Nivolumab, Ipilimumab, Cabozantinib

\*Enrollment to the triplet arm was discontinued by protocol amendment

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type BIOLOGICAL

Specified dose on specified days

Interventions

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Nivolumab

Specified dose on specified day

Intervention Type BIOLOGICAL

Cabozantinib

Specified dose on specified days

Intervention Type DRUG

Sunitinib

Specified dose on specified days.

Intervention Type DRUG

Ipilimumab

Specified dose on specified days

Intervention Type BIOLOGICAL

Other Intervention Names

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Opdivo BMS-936558 Cabometyx Sutent Yervoy BMS-734016

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Exelixis

INDUSTRY

Sponsor Role collaborator

Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0077

Daphne, Alabama, United States

Site Status

Local Institution - 0044

Goodyear, Arizona, United States

Site Status

Local Institution - 0132

Tucson, Arizona, United States

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Local Institution - 0133

Bakersfield, California, United States

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Local Institution - 0093

Los Angeles, California, United States

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Local Institution - 0090

Redondo Beach, California, United States

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Local Institution - 0088

San Luis Obispo, California, United States

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Central Coast Medical Oncology Corporation

Santa Maria, California, United States

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Local Institution - 0103

Aurora, Colorado, United States

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Local Institution - 0127

Athens, Georgia, United States

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Local Institution - 0086

Newnan, Georgia, United States

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Local Institution - 0036

Chicago, Illinois, United States

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Local Institution - 0042

Zion, Illinois, United States

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Local Institution - 0091

Fort Wayne, Indiana, United States

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Local Institution - 0087

Wichita, Kansas, United States

Site Status

Local Institution - 0113

Boston, Massachusetts, United States

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Local Institution - 0037

Boston, Massachusetts, United States

Site Status

Local Institution - 0106

Kansas City, Missouri, United States

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Local Institution - 0035

St Louis, Missouri, United States

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Local Institution - 0102

Las Vegas, Nevada, United States

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Local Institution - 0040

Buffalo, New York, United States

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Local Institution - 0017

New York, New York, United States

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Local Institution - 0067

Portland, Oregon, United States

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Local Institution - 0135

Allentown, Pennsylvania, United States

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Local Institution - 0105

Nashville, Tennessee, United States

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Local Institution - 0080

Austin, Texas, United States

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Local Institution - 0075

Dallas, Texas, United States

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Local Institution - 0068

Houston, Texas, United States

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Local Institution - 0078

Sherman, Texas, United States

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Local Institution - 0131

Norfolk, Virginia, United States

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Local Institution - 0046

CABA, Buenos Aires, Argentina

Site Status

Local Institution - 0048

Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina

Site Status

Local Institution - 0114

Viedma, Río Negro Province, Argentina

Site Status

Local Institution - 0138

CABA, , Argentina

Site Status

Local Institution - 0050

Córdoba, , Argentina

Site Status

Local Institution - 0049

Córdoba, , Argentina

Site Status

Local Institution - 0047

San Miguel de Tucumán, , Argentina

Site Status

Local Institution - 0002

North Ryde, New South Wales, Australia

Site Status

Local Institution - 0008

Sydney, New South Wales, Australia

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Local Institution - 0009

Sydney, New South Wales, Australia

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Local Institution - 0073

Westmead, New South Wales, Australia

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Local Institution - 0006

Herston, Queensland, Australia

Site Status

Local Institution - 0001

Southport, Queensland, Australia

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Local Institution - 0004

Elizabeth Vale, South Australia, Australia

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Local Institution - 0005

Malvern, Victoria, Australia

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Local Institution - 0007

Doubleview, Western Australia, Australia

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Local Institution - 0129

South Brisbane, , Australia

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Local Institution - 0057

Belo Horizonte, Minas Gerais, Brazil

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Local Institution - 0119

Ijuí, Rio Grande do Sul, Brazil

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Local Institution - 0056

Porto Alegre, Rio Grande do Sul, Brazil

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Local Institution - 0060

Porto Alegre, Rio Grande do Sul, Brazil

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Local Institution - 0058

Barretos, São Paulo, Brazil

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Local Institution - 0066

Rio de Janeiro, , Brazil

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Local Institution - 0074

São Paulo, , Brazil

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Local Institution - 0061

São Paulo, , Brazil

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Local Institution - 0045

Santiago, Santiago Metropolitan, Chile

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Local Institution - 0034

Hradec Králové, , Czechia

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Local Institution - 0033

Olomouc, , Czechia

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Local Institution - 0013

Aachen, , Germany

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Local Institution - 0016

Bonn, , Germany

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Local Institution - 0117

Essen, , Germany

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Local Institution - 0023

Jena, , Germany

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Local Institution - 0010

München, , Germany

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Local Institution - 0014

Nuremberg, , Germany

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Local Institution - 0011

Tübingen, , Germany

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Local Institution - 0082

Athens, , Greece

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Local Institution - 0083

Thessaloniki, , Greece

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Local Institution - 0072

Haifa, , Israel

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Local Institution - 0070

Kfar Saba, , Israel

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Local Institution - 0071

Petah Tikva, , Israel

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Local Institution - 0069

Ramat Gan, , Israel

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Local Institution - 0054

Arezzo, , Italy

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Local Institution - 0052

Milan, , Italy

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Local Institution - 0055

Napoli, , Italy

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Local Institution - 0053

Padua, , Italy

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Local Institution - 0051

Pavia, , Italy

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Local Institution - 0147

Pavia, , Italy

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Local Institution - 0172

Terni, , Italy

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Local Institution - 0148

Akita, Akita, Japan

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Local Institution - 0156

Hirosaki, Aomori, Japan

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Local Institution - 0164

Sapporo, Hokkaido, Japan

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Local Institution - 0157

Sapporo, Hokkaido, Japan

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Local Institution - 0168

Kobe, Hyōgo, Japan

Site Status

Local Institution - 0159

Morioka, Iwate, Japan

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Local Institution - 0171

Yokohama, Kanagawa, Japan

Site Status

Local Institution - 0166

Yokohama, Kanagawa, Japan

Site Status

Local Institution - 0150

Niigata, Niigata, Japan

Site Status

Local Institution - 0169

Okayama, Okayama-ken, Japan

Site Status

Local Institution - 0170

Osaka, Osaka, Japan

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Local Institution - 0160

Osakasayamashi, Osaka, Japan

Site Status

Local Institution - 0163

Suita-shi, Osaka, Japan

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Local Institution - 0154

Osaka, Osaka-shi, Japan

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Local Institution - 0155

Hidaka-shi, Saitama, Japan

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Local Institution - 0153

Tokushima, Tokushima, Japan

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Local Institution - 0152

Adachi-ku, Tokyo, Japan

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Local Institution - 0158

Bunkyo-ku, Tokyo, Japan

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Local Institution - 0151

Bunkyo-ku, Tokyo, Japan

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Local Institution - 0173

Minato-ku, Tokyo, Japan

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Local Institution - 0167

Chiba, , Japan

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Local Institution - 0161

Fukuoka, , Japan

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Local Institution - 0162

Nagasaki, , Japan

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Local Institution - 0149

Tokyo, , Japan

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Local Institution - 0165

Yamagata, , Japan

Site Status

Local Institution - 0108

Zapopan, Jalisco, Mexico

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Local Institution - 0062

Mexico City, Mexico City, Mexico

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Local Institution - 0116

Mexico City, Mexico City, Mexico

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Local Institution - 0115

Tlalpan, Mexico City, Mexico

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Local Institution - 0065

Monterrey, Nuevo León, Mexico

Site Status

Local Institution - 0143

Monterrey, Nuevo León, Mexico

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Local Institution - 0064

Monterrey, Nuevo León, Mexico

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Local Institution - 0063

Querétaro City, Querétaro, Mexico

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Local Institution - 0136

Mérida, Yucatán, Mexico

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Local Institution - 0084

Biała Podlaska, , Poland

Site Status

Local Institution - 0130

Bydgoszcz, , Poland

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Local Institution - 0085

Gdansk, , Poland

Site Status

Local Institution - 0021

Cluj-Napoca, , Romania

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Local Institution - 0022

Craiova, , Romania

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Local Institution - 0020

Moscow, , Russia

Site Status

Local Institution - 0099

Saint Petersburg, , Russia

Site Status

Local Institution - 0125

Barcelona, , Spain

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Local Institution - 0121

Madrid, , Spain

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Local Institution - 0120

Madrid, , Spain

Site Status

Local Institution - 0144

Santander, , Spain

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Local Institution - 0124

Seville, , Spain

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Local Institution - 0123

Valencia, , Spain

Site Status

Local Institution - 0107

Ankara, , Turkey (Türkiye)

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Local Institution - 0139

Ankara, , Turkey (Türkiye)

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Local Institution - 0094

Ankara, , Turkey (Türkiye)

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Local Institution - 0096

Antalya, , Turkey (Türkiye)

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Local Institution - 0097

Denizli, , Turkey (Türkiye)

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Local Institution - 0095

Edirne, , Turkey (Türkiye)

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Local Institution - 0146

Istanbul, , Turkey (Türkiye)

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Local Institution - 0111

London, , United Kingdom

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Local Institution - 0109

Manchester, , United Kingdom

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Local Institution - 0140

Truro, , United Kingdom

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Countries

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United States Argentina Australia Brazil Chile Czechia Germany Greece Israel Italy Japan Mexico Poland Romania Russia Spain Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39452894 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38642472 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37431849 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37146227 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36625894 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36327527 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35688173 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35032437 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34980597 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33657295 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33058158 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2017-000759-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-9ER

Identifier Type: -

Identifier Source: org_study_id

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