BMS-936558 (MDX-1106) In Subjects With Advanced/Metastatic Clear-Cell Renal Cell Carcinoma (RCC)

Study Overview
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Brief Summary
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The purpose of this study is to measure how active BMS-936558 (nivolumab) is against Renal Cell Carcinoma (RCC) as measured by the disease not progressing and whether a dose response relationship exists.

Official Title
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A Randomized, Blinded, Phase 2 Dose-Ranging Study Of BMS-936558 (MDX-1106) In Subjects With Progressive, Advanced/Metastatic Clear-Cell Renal Cell Carcinoma Who Have Received Prior Anti-Angiogenic Therapy

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Biological: nivolumab
* Biological: nivolumab
* Biological: nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic confirmation of Renal cell carcinoma (RCC) with a clear cell component Previous treatment with at least one anti-angiogenic agent Progressed within 6 months of study enrollment Subjects should not have had more than 3 prior treatments for locally advanced or metastatic disease Must have available tumor tissue for submission Subjects must also meet various laboratory parameters for inclusion Exclusion Criteria: Subjects with any active autoimmune disease or a history of known autoimmune disease Other protocol-defined inclusion/exclusion criteria 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: nivolumab - 0.3 mg/kg<br> | Biological: nivolumab<br>* Solution, Intravenous (IV), 0.3 mg/kg, every 3 weeks (Q 3 weeks), Until Progressive disease (PD), toxicity or discontinue for other reasons<br>* Other names: BMS-936558;|
| Experimental: Arm 2: nivolumab - 2.0 mg/kg<br> | Biological: nivolumab<br>* Solution, Intravenous (IV), 2.0 mg/kg, every 3 weeks (Q 3 weeks), Until Progressive disease (PD), toxicity or discontinue for other reasons<br>* Other names: BMS-936558;|
| Experimental: Arm 3: nivolumab - 10.0 mg/kg<br> | Biological: nivolumab<br>* Solution, Intravenous (IV), 10.0 mg/kg, every 3 weeks (Q 3 weeks), Until Progressive disease (PD), toxicity or discontinue for other reasons<br>* Other names: BMS-936558;|

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 randomization to date of first disease progression (either clinical or radiographic progression, as assessed by the investigator). Tumor assessments (radiographic scans) were done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression. Survival was assessed every 3 months. The analysis of PFS was conducted after approximately 116 events (progression or death), approximately 2 years. PFS was calculated based on investigator's assessment of first date of progression (either clinical or radiographic progression) or date of death if progression did not occur. Progression was at least a 20% increase in the sum of diameters of the longest target lesions since screening (the sum must be an absolute increase of at least 5 mm), or measurable increase in non-target lesion or appearance of one or more new lesions. | From randomization to disease progression or death (up to approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate (BORR) | BORR is defined as the percentage of participants whose best response is either partial response (PR) or complete response (CR). Tumor response was evaluated by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 80% confidence interval is based on the Clopper and Pearson method | From randomization until disease progression or discontinuation of study therapy (up to approximately 2 years) | 
| Overall Survival (OS) | OS is defined as the time from date of randomization until date of death. If the participant did not die, overall survival will be censored on the last date the participant was known to be alive. Survival status is collected at each visit during treatment and every 3 months during follow-up. OS is based on Kaplan-Meier estimates. | From randomization to to date of death (up to approximately 8 years) | 
| Number of Participants Experiencing Adverse Events | Number of participants experiencing different types of events, including Adverse Events (AEs), Drug-related AEs, AEs leading to discontinuation, Drug-related AEs leading to discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs. Events are classified based on the NCI Common Terminology Criteria (CTC) version 4.0 | From first dose to 30 days following last dose (up to approximately 6 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced/Metastatic, clear cell component