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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03141177




Registration number
NCT03141177
Ethics application status
Date submitted
3/05/2017
Date registered
4/05/2017
Date last updated
17/01/2024

Titles & IDs
Public title
A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
Scientific 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
Secondary ID [1] 0 0
2017-000759-20
Secondary ID [2] 0 0
CA209-9ER
Universal Trial Number (UTN)
Trial acronym
CheckMate 9ER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Nivolumab
Treatment: Drugs - Cabozantinib
Treatment: Drugs - Sunitinib
Treatment: Other - Ipilimumab

Experimental: Doublet - Nivolumab and Cabozantinib

Active comparator: Monotherapy - Sunitinib

Experimental: Triplet - Nivolumab, Ipilimumab, Cabozantinib

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


Treatment: Other: Nivolumab
Specified dose on specified day

Treatment: Drugs: Cabozantinib
Specified dose on specified days

Treatment: Drugs: Sunitinib
Specified dose on specified days.

Treatment: Other: Ipilimumab
Specified dose on specified days
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
From randomization date to date of first documented tumor progression or death, whichever occurs first (Up to 31 months)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization date to death date (Up to 31 months)
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
Up to 31 Months
Secondary outcome [3] 0 0
Number of Participants Experiencing Adverse Events (AEs)
Timepoint [3] 0 0
From first dose to 100 days following last dose (Up to 32 Months)
Secondary outcome [4] 0 0
Number of Participants Experiencing Serious Adverse Events (SAEs)
Timepoint [4] 0 0
From first to dose to 100 days following last dose (Up to 32 months)
Secondary outcome [5] 0 0
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Timepoint [5] 0 0
From first dose to 30 days following last dose (Up to 30 months)
Secondary outcome [6] 0 0
Number of Deaths
Timepoint [6] 0 0
From first dose to (up to 31 months) following first dose
Secondary outcome [7] 0 0
Number of Participants With Laboratory Abnormalities
Timepoint [7] 0 0
From first dose to 30 days following last dose (Up to 30 Months)
Secondary outcome [8] 0 0
Number of Participants With Laboratory Values Grade Shifting From Baseline
Timepoint [8] 0 0
From first dose to 30 days following last dose (Up to 30 Months)

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



* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
17/04/2024
Actual
Sample size
Target
Accrual to date
Final
701
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - 0002 - North Ryde
Recruitment hospital [2] 0 0
Local Institution - 0008 - Sydney
Recruitment hospital [3] 0 0
Local Institution - 0009 - Sydney
Recruitment hospital [4] 0 0
Local Institution - 0073 - Westmead
Recruitment hospital [5] 0 0
Local Institution - 0006 - Herston
Recruitment hospital [6] 0 0
Local Institution - 0001 - Southport
Recruitment hospital [7] 0 0
Local Institution - 0004 - Elizabeth Vale
Recruitment hospital [8] 0 0
Local Institution - 0005 - Malvern
Recruitment hospital [9] 0 0
Local Institution - 0007 - Doubleview
Recruitment hospital [10] 0 0
Local Institution - 0129 - South Brisbane
Recruitment postcode(s) [1] 0 0
0 - North Ryde
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
2139 - Sydney
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
4006 - Herston
Recruitment postcode(s) [6] 0 0
4215 - Southport
Recruitment postcode(s) [7] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [8] 0 0
3144 - Malvern
Recruitment postcode(s) [9] 0 0
6018 - Doubleview
Recruitment postcode(s) [10] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
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California
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Colorado
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Georgia
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Illinois
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Indiana
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Kansas
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Massachusetts
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Missouri
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Virginia
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Argentina
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Buenos Aires
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Argentina
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RIO Negro
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Argentina
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Caba
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Argentina
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Cordoba
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Argentina
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Tucuman
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Brazil
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Minas Gerais
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Brazil
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Sao Paulo
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Brazil
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Rio De Janeiro
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Chile
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Metropolitana
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Czechia
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Hradec Kralove
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Czechia
State/province [29] 0 0
Olomouc
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Germany
State/province [30] 0 0
Aachen
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Germany
State/province [31] 0 0
Bonn
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Germany
State/province [32] 0 0
Essen
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Germany
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Jena
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Germany
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Muenchen
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Germany
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Nuernberg
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Germany
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Tuebingen
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Greece
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Athens
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Greece
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Thessaloniki
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Israel
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Haifa
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Israel
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Kfar Saba
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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Italy
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Arezzo
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Milano
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Italy
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Napoli
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Italy
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Padova
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Italy
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Pavia
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Italy
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Terni
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Japan
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Akita
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Hokkaido
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Hyogo
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Iwate
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Kanagawa
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Japan
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Niigata
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Japan
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Okayama
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Japan
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Osaka-shi
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Tokushima
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Japan
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Tokyo
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Japan
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Aomori
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Japan
State/province [62] 0 0
Chiba
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Japan
State/province [63] 0 0
Fukuoka
Country [64] 0 0
Japan
State/province [64] 0 0
Nagasaki
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Japan
State/province [65] 0 0
Yamagata
Country [66] 0 0
Mexico
State/province [66] 0 0
Distrito Federal
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Mexico
State/province [67] 0 0
Jalisco
Country [68] 0 0
Mexico
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Nuevo Leon
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Mexico
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Nuevo LEON
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Mexico
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Yucatan
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Mexico
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Queretaro
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Poland
State/province [72] 0 0
Biala Podlaska
Country [73] 0 0
Poland
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Bydgoszcz
Country [74] 0 0
Poland
State/province [74] 0 0
Gdansk
Country [75] 0 0
Romania
State/province [75] 0 0
Cluj-Napoca
Country [76] 0 0
Romania
State/province [76] 0 0
Craiova
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Moscow
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Saint-Petersburg
Country [79] 0 0
Spain
State/province [79] 0 0
Barcelona
Country [80] 0 0
Spain
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Madrid
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Santander
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Spain
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Sevilla
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Spain
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Valencia
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Turkey
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Ankara
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Turkey
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Antalya
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Turkey
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Denizli
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Turkey
State/province [87] 0 0
Edirne
Country [88] 0 0
Turkey
State/province [88] 0 0
Istanbul
Country [89] 0 0
United Kingdom
State/province [89] 0 0
London
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Manchester
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Exelixis
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Ono Pharmaceutical Co. Ltd
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT03141177
Trial related presentations / publications
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.
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. Erratum In: Lancet Oncol. 2022 Jul;23(7):e319. doi: 10.1016/S1470-2045(22)00346-1. Lancet Oncol. 2022 Sep;23(9):e404. doi: 10.1016/S1470-2045(22)00511-3.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03141177