A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 9ER)

• ClinicalTrials.gov Identifier: NCT03141177
• Recruitment Status: Active, not recruiting
• First Posted: May 4, 2017
• Results First Posted: April 26, 2022
• Last Update Posted: January 17, 2024
• Sponsor: Bristol-Myers Squibb
• Collaborators: Exelixis; Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: May 3, 2017
• First Posted Date: May 4, 2017
• Results First Submitted Date: February 11, 2022
• Results First Posted Date: April 26, 2022
• Last Update Posted Date: January 17, 2024
• Actual Study Start Date: August 22, 2017
• Actual Primary Completion Date: February 12, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2022)

Progression Free Survival (PFS) [ Time Frame: From randomization date to date of first documented tumor progression or death, whichever occurs first (Up to 31 months) ]

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

Original Primary Outcome Measures (submitted: May 3, 2017)

• Progression Free Survival (PFS) per blinded independent central review (BICR) of Arm A versus Arm C [ Time Frame: Up to 22 months ]
  Intermediate/poor risk randomized participants
• PFS per BICR of Arm B versus Arm C [ Time Frame: Up to 22 months ]
  Intermediate/poor risk randomized participants

Current Secondary Outcome Measures (submitted: March 29, 2022)

• Overall Survival (OS) [ Time Frame: From randomization date to death date (Up to 31 months) ]
  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").
• Objective Response Rate (ORR) [ Time Frame: Up to 31 Months ]
  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.
• Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: From first dose to 100 days following last dose (Up to 32 Months) ]
  Number of participants experiencing various types of any grade adverse events (AEs) during the specified time frame.
• Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: From first to dose to 100 days following last dose (Up to 32 months) ]
  Number of participants experiencing various types of any grade serious adverse events (SAEs) during the specified time frame.
• Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation [ Time Frame: From first dose to 30 days following last dose (Up to 30 months) ]
  Number of participants experiencing various types of any grade adverse events (AEs) leading to discontinuation during the specified time frame.
• Number of Deaths [ Time Frame: From first dose to (up to 31 months) following first dose ]
  Number of deaths due to any cause during the specified time frame.
• Number of Participants With Laboratory Abnormalities [ Time Frame: From first dose to 30 days following last dose (Up to 30 Months) ]
  Number of participants experiencing laboratory abnormalities in hematology, serum chemistry and electrolytes with grade 3 or higher during the specified time frame.
• Number of Participants With Laboratory Values Grade Shifting From Baseline [ Time Frame: From first dose to 30 days following last dose (Up to 30 Months) ]
  Number of participants experiencing worsening shift from baseline in any grade and grade 3-4 of laboratory values during the specified time frame.

Original Secondary Outcome Measures (submitted: May 3, 2017)

• PFS per BICR of Arm A versus Arm C [ Time Frame: Up to 22 months ]
  In all randomized participants
• PFS per BICR of Arm B versus Arm C [ Time Frame: Up to 22 months ]
  In all randomized participants
• Overall Survival (OS) of Arm A versus Arm C [ Time Frame: Up to 34 months ]
  In all intermediate/poor risk randomized participants
• OS of Arm B versus Arm C [ Time Frame: Up to 34 months ]
  In all intermediate/poor risk randomized participants
• OS of Arm A versus Arm C [ Time Frame: Up to 34 months ]
  In all randomized participants
• OS of Arm B versus Arm C [ Time Frame: Up to 34 months ]
  In all randomized participants
• Objective Response Rate (ORR) [ Time Frame: Approximately 16 months ]
  In all intermediate/poor risk randomized and all randomized participants
• Incidence of adverse events (AEs) [ Time Frame: Up to 34 months ]
  Safety and Tolerability
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 34 months ]
  Safety and Tolerability

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Renal Cell Carcinoma

Intervention

• Biological: Nivolumab
  Specified dose on specified day
  Other Names:

  • Opdivo
  • BMS-936558
• Drug: Cabozantinib
  Specified dose on specified days
  Other Name: Cabometyx
• Drug: Sunitinib
  Specified dose on specified days.
  Other Name: Sutent
• Biological: Ipilimumab
  Specified dose on specified days
  Other Names:

  • Yervoy
  • BMS-734016

Study Arms

• Experimental: Doublet
  Nivolumab and Cabozantinib
  Interventions:

  • Biological: Nivolumab
  • Drug: Cabozantinib
• Active Comparator: Monotherapy
  Sunitinib
  Intervention: Drug: Sunitinib
• Experimental: Triplet

  Nivolumab, Ipilimumab, Cabozantinib

  *Enrollment to the triplet arm was discontinued by protocol amendment

  Intervention: Biological: Ipilimumab

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. Lancet Oncol. 2022 Sep;23(9):e404.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 13, 2021): 701
• Original Estimated Enrollment (submitted: May 3, 2017): 1014
• Estimated Study Completion Date: April 17, 2024
• Actual Primary Completion Date: February 12, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Brazil, Chile, Czechia, Germany, Greece, Israel, Italy, Japan, Mexico, Poland, Romania, Russian Federation, Spain, Turkey, United Kingdom, United States
• Removed Location Countries: France

Administrative Information

• NCT Number: NCT03141177
• Other Study ID Numbers: CA209-9ER; 2017-000759-20 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current

Collaborators

• Exelixis
• Ono Pharmaceutical Co. Ltd

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: January 2024