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

Study Overview
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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

Official Title
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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

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Biological: Nivolumab
* Drug: Cabozantinib
* Drug: Sunitinib
* Biological: Ipilimumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doublet<br>Nivolumab and Cabozantinib | Biological: Nivolumab<br>* Specified dose on specified day<br>* Other names: BMS-936558;Drug: Cabozantinib<br>* Specified dose on specified days<br>* Other names: Cabometyx;|
| Active Comparator: Monotherapy<br>Sunitinib | Drug: Sunitinib<br>* Specified dose on specified days.<br>* Other names: Sutent;|
| Experimental: Triplet<br>Nivolumab, Ipilimumab, Cabozantinib *Enrollment to the triplet arm was discontinued by protocol amendment | Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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