An Investigational Immuno-Therapy Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety and efficacy of different administration regimens of nivolumab plus ipilimumab in subjects with renal cell carcinoma.

Official Title
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Phase II, Randomized, Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Biological: Opdivo
* Biological: Yervoy


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: Advanced Renal Cell Carcinoma Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work Must have at least 1 lesion with measurable disease Exclusion Criteria: Subjects with active central nervous system metastases Subjects who received prior therapy with checkpoint inhibitor Subjects with active, known or suspected autoimmune disease 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: Co-Administration<br>Nivolumab and Ipilimumab Co-Administration | Biological: Opdivo<br>* Specified dose on specified days<br>* Other names: Nivolumab;Biological: Yervoy<br>* Specified dose on specified days<br>* Other names: Ipilimumab;|
| Experimental: Sequential Administration<br>Nivolumab and Ipilimumab Sequential Administration | Biological: Opdivo<br>* Specified dose on specified days<br>* Other names: Nivolumab;Biological: Yervoy<br>* Specified dose on specified days<br>* Other names: Ipilimumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participant With Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Within 2 Days After Any Dose in the Combination Period | The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1). | From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participant With Adverse Events in the Narrow Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Occurring Within 2 Days After Any Dose in the Combination Period | The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction narrow scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1). | From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months) | 
| The Percentage of Participants With Drug Related Grade 3-5 Adverse Events | The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher, judged to be related to study treatment by the investigator, with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria. | From first dose to 30 days after last dose of study therapy (up to approximately 48 months) | 
| The Percentage of Participants With All Causality Grade 3-5 Adverse Events | The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using the NCI CTCAE version 4.0 criteria | From first dose to 30 days after last dose of study therapy (up to approximately 48 months) | 
| Objective Response Rate (ORR) | The percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Complete Response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From randomization to the date of objectively documented progression or the date of first subsequent anti-cancer (up to approximately 52 months) | 
| Progression Free Survival (PFS) | The time between the date of randomization and the first date of documented progression, or death due to any cause, whichever occurs first (per investigator). Participants who die without progression will be considered to have progressed on the date of their death. Participants who did not progress or die are censored on the date of their last evaluable tumor assessment. Participants with no on study tumor assessments and who did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression) | From randomization to the first date of documented progression or death due to any cause (up to approximately 52 months) | 
| Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab | Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized prior to the next dose (predose). 1 Cycle = 3 weeks | pre-dose on day 1 of cycle 2 and 4 | 
| Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab | Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized at the end of infusion (EOI). 1 Cycle = 3 weeks | EOI on day 1 of cycle 1, 2, and 4 |