Clinical trial NCT03141177: A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Renal Cell Carcinoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Exelixis
name: Ono Pharmaceutical Co. Ltd
First posted: 2017-05-04
Enrollment: 701
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

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

Other protocol defined inclusion/exclusion criteria could apply

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization date to date of first documented tumor progression or death, whichever occurs first (Up to 31 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization date to death date (Up to 31 months)
measure: Objective Response Rate (ORR)
timeFrame: Up to 31 Months
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From first dose to 100 days following last dose (Up to 32 Months)
measure: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: From first to dose to 100 days following last dose (Up to 32 months)
measure: Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
timeFrame: From first dose to 30 days following last dose (Up to 30 months)
measure: Number of Deaths
timeFrame: From first dose to (up to 31 months) following first dose
measure: Number of Participants With Laboratory Abnormalities
timeFrame: From first dose to 30 days following last dose (Up to 30 Months)
measure: Number of Participants With Laboratory Values Grade Shifting From Baseline
timeFrame: From first dose to 30 days following last dose (Up to 30 Months)
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Local Institution - 0077
state: Alabama
city: Goodyear
country: United States
facility: Local Institution - 0044
state: Arizona
city: Tucson
country: United States
facility: Local Institution - 0132
state: Arizona
city: Bakersfield
country: United States
facility: Local Institution - 0133
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0093
state: California
city: Redondo Beach
country: United States
facility: Local Institution - 0090
state: California
city: San Luis Obispo
country: United States
facility: Local Institution - 0088
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Aurora
country: United States
facility: Local Institution - 0103
state: Colorado
city: Athens
country: United States
facility: Local Institution - 0127
state: Georgia
city: Newnan
country: United States
facility: Local Institution - 0086
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0036
state: Illinois
city: Zion
country: United States
facility: Local Institution - 0042
state: Illinois
city: Fort Wayne
country: United States
facility: Local Institution - 0091
state: Indiana
city: Wichita
country: United States
facility: Local Institution - 0087
state: Kansas
city: Boston
country: United States
facility: Local Institution - 0113
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0037
state: Massachusetts
city: Kansas City
country: United States
facility: Local Institution - 0106
state: Missouri
city: Saint Louis
country: United States
facility: Local Institution - 0035
state: Missouri
city: Las Vegas
country: United States
facility: Local Institution - 0102
state: Nevada
city: Buffalo
country: United States
facility: Local Institution - 0040
state: New York
city: New York
country: United States
facility: Local Institution - 0017
state: New York
city: Portland
country: United States
facility: Local Institution - 0067
state: Oregon
city: Allentown
country: United States
facility: Local Institution - 0135
state: Pennsylvania
city: Nashville
country: United States
facility: Local Institution - 0105
state: Tennessee
city: Austin
country: United States
facility: Local Institution - 0080
state: Texas
city: Dallas
country: United States
facility: Local Institution - 0075
state: Texas
city: Houston
country: United States
facility: Local Institution - 0068
state: Texas
city: Sherman
country: United States
facility: Local Institution - 0078
state: Texas
city: Norfolk
country: United States
facility: Local Institution - 0131
state: Virginia
city: Caba
country: Argentina
facility: Local Institution - 0046
state: Buenos Aires
city: Ciudad Autonoma De Buenos Aire
country: Argentina
facility: Local Institution - 0048
state: Buenos Aires
city: Viedma
country: Argentina
facility: Local Institution - 0114
state: RIO Negro
city: Caba
country: Argentina
facility: Local Institution - 0138
city: Cordoba
country: Argentina
facility: Local Institution - 0050
city: Cordoba
country: Argentina
facility: Local Institution - 0049
city: Tucuman
country: Argentina
facility: Local Institution - 0047
city: North Ryde
country: Australia
facility: Local Institution - 0002
state: New South Wales
city: Sydney
country: Australia
facility: Local Institution - 0008
state: New South Wales
city: Sydney
country: Australia
facility: Local Institution - 0009
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution - 0073
state: New South Wales
city: Herston
country: Australia
facility: Local Institution - 0006
state: Queensland
city: Southport
country: Australia
facility: Local Institution - 0001
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Local Institution - 0004
state: South Australia
city: Malvern
country: Australia
facility: Local Institution - 0005
state: Victoria
city: Doubleview
country: Australia
facility: Local Institution - 0007
state: Western Australia
city: South Brisbane
country: Australia
facility: Local Institution - 0129
city: Belo Horizonte
country: Brazil
facility: Local Institution - 0057
state: Minas Gerais
city: Ijui
country: Brazil
facility: Local Institution - 0119
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0056
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0060
state: RIO Grande DO SUL
city: Barretos
country: Brazil
facility: Local Institution - 0058
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution - 0066
city: Sao Paulo
country: Brazil
facility: Local Institution - 0074
city: Sao Paulo
country: Brazil
facility: Local Institution - 0061
city: Santiago
country: Chile
facility: Local Institution - 0045
state: Metropolitana
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0034
city: Olomouc
country: Czechia
facility: Local Institution - 0033
city: Aachen
country: Germany
facility: Local Institution - 0013
city: Bonn
country: Germany
facility: Local Institution - 0016
city: Essen
country: Germany
facility: Local Institution - 0117
city: Jena
country: Germany
facility: Local Institution - 0023
city: Muenchen
country: Germany
facility: Local Institution - 0010
city: Nuernberg
country: Germany
facility: Local Institution - 0014
city: Tuebingen
country: Germany
facility: Local Institution - 0011
city: Athens
country: Greece
facility: Local Institution - 0082
city: Thessaloniki
country: Greece
facility: Local Institution - 0083
city: Haifa
country: Israel
facility: Local Institution - 0072
city: Kfar Saba
country: Israel
facility: Local Institution - 0070
city: Petah Tikva
country: Israel
facility: Local Institution - 0071
city: Ramat Gan
country: Israel
facility: Local Institution - 0069
city: Arezzo
country: Italy
facility: Local Institution - 0054
city: Milano
country: Italy
facility: Local Institution - 0052
city: Napoli
country: Italy
facility: Local Institution - 0055
city: Padova
country: Italy
facility: Local Institution - 0053
city: Pavia
country: Italy
facility: Local Institution - 0051
city: Pavia
country: Italy
facility: Local Institution - 0147
city: Terni
country: Italy
facility: Local Institution - 0172
city: Akita-shi
country: Japan
facility: Local Institution - 0148
state: Akita
city: Hirosaki
country: Japan
facility: Local Institution - 0156
state: Aomori
city: Sapporo-shi
country: Japan
facility: Local Institution - 0157
state: Hokkaido
city: Sapporo
country: Japan
facility: Local Institution - 0164
state: Hokkaido
city: Kobe
country: Japan
facility: Local Institution - 0168
state: Hyogo
city: Morioka
country: Japan
facility: Local Institution - 0159
state: Iwate
city: Yokohama
country: Japan
facility: Local Institution - 0171
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution - 0166
state: Kanagawa
city: Niigata-shi
country: Japan
facility: Local Institution - 0150
state: Niigata
city: Okayama-shi
country: Japan
facility: Local Institution - 0169
state: Okayama
city: Osaka
country: Japan
facility: Local Institution - 0154
state: Osaka-shi
city: Osaka-shi
country: Japan
facility: Local Institution - 0170
state: Osaka
city: Osakasayamashi
country: Japan
facility: Local Institution - 0160
state: Osaka
city: Suita-shi
country: Japan
facility: Local Institution - 0163
state: Osaka
city: Hidaka-shi
country: Japan
facility: Local Institution - 0155
state: Saitama
city: Tokushima-shi
country: Japan
facility: Local Institution - 0153
state: Tokushima
city: Adachi-ku
country: Japan
facility: Local Institution - 0152
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0158
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0151
state: Tokyo
city: Minato-ku
country: Japan
facility: Local Institution - 0173
state: Tokyo
city: Chiba
country: Japan
facility: Local Institution - 0167
city: Fukuoka
country: Japan
facility: Local Institution - 0161
city: Nagasaki
country: Japan
facility: Local Institution - 0162
city: Tokyo
country: Japan
facility: Local Institution - 0149
city: Yamagata
country: Japan
facility: Local Institution - 0165
city: Ciudad de Mexico
country: Mexico
facility: Local Institution - 0062
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution - 0116
state: Distrito Federal
city: Tlalpan
country: Mexico
facility: Local Institution - 0115
state: Distrito Federal
city: Zapopan
country: Mexico
facility: Local Institution - 0108
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 0065
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution - 0143
state: Nuevo LEON
city: Monterrey
country: Mexico
facility: Local Institution - 0064
state: Nuevo Leon
city: Santiago de Queretaro
country: Mexico
facility: Local Institution - 0063
state: Querétaro
city: Merida
country: Mexico
facility: Local Institution - 0136
state: Yucatan
city: Biala Podlaska
country: Poland
facility: Local Institution - 0084
city: Bydgoszcz
country: Poland
facility: Local Institution - 0130
city: Gdansk
country: Poland
facility: Local Institution - 0085
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0021
city: Craiova
country: Romania
facility: Local Institution - 0022
city: Moscow
country: Russian Federation
facility: Local Institution - 0020
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution - 0099
city: Barcelona
country: Spain
facility: Local Institution - 0125
city: Madrid
country: Spain
facility: Local Institution - 0121
city: Madrid
country: Spain
facility: Local Institution - 0120
city: Santander
country: Spain
facility: Local Institution - 0144
city: Sevilla
country: Spain
facility: Local Institution - 0124
city: Valencia
country: Spain
facility: Local Institution - 0123
city: Ankara
country: Turkey
facility: Local Institution - 0107
city: Ankara
country: Turkey
facility: Local Institution - 0139
city: Ankara
country: Turkey
facility: Local Institution - 0094
city: Antalya
country: Turkey
facility: Local Institution - 0096
city: Denizli
country: Turkey
facility: Local Institution - 0097
city: Edirne
country: Turkey
facility: Local Institution - 0095
city: Istanbul
country: Turkey
facility: Local Institution - 0146
city: London
country: United Kingdom
facility: Local Institution - 0111
city: Manchester
country: United Kingdom
facility: Local Institution - 0109
city: Truro
country: United Kingdom
facility: Local Institution - 0140
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.