A Study of Combination Nivolumab and Ipilimumab Retreatment in Patients With Advanced Renal Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of the study is to assess the effectiveness of re-induction with Nivolumab combined with ipilimumab.

Official Title
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A Phase 2, Single-arm Open-label Study of Combination Nivolumab and Ipilimumab Retreatment in Advanced Renal Cell Carcinoma Patients Progressing on Nivolumab Maintenance Therapy After Nivolumab and Ipilimumab Induction

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Participants and Target Disease Characteristics- - Confirmed disease progression by RECIST 1.1 criteria on nivolumab maintenance after induction with ipilimumab and nivolumab Progress of maintenance treatment of nivolumab by RECIST. Pathology report must be submitted for embedded tissue block or tumor tissue. Age and Reproduction Sexually active males with WOCBP must agree to instructions for contraception and fetal protection. WOCBP need to use contraception throughout the study and for 5 months post treatment. Exclusion Criteria autoimmune disease statement Active central nervous system metastases Participants with an active autoimmune disease, diabetes mellitus, skin disorders, hyperthyroidism requiring hormone treatments are permitted to enroll. Any major surgery 28 days before 1st treatment Concomitant Therapy participants that have received a live vaccine within 30 days of treatment. use of investigational agent or device with in 28 days before first dosage study treatment. Physical and Laboratory Test Findings Allergies and Adverse Drug Reaction Age and Reproduction

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab + Ipilimumab (combination)<br>Nivolumab + Ipilimumab (combination) Q3W for 4 doses | Biological: Nivolumab<br>* Specific dose on specific days<br>* Other names: Opdivo;Biological: Ipilimumab<br>* Specific dose on specific days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Disease Control Rate (DCR) is defined as the percentage of participants who achieve a confirmed best response of complete response (CR), partial response (PR), or stable disease (SD) for at least 6 months after first treatment dose per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. | From first dose up to approximately 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from first dose to the date of death from any cause. For participants that are alive, their survival time will be censored at the date of last contact (last known alive date). OS will be censored for participants at the date of first dose if they were treated but had no follow-up. | From first dose to the date of death from any cause (up to approximately 14 months) | 
| Overall Response Rate (ORR) | Overall Response Rate (ORR) is defined as the percentage of participants who achieve a best response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From first dose and the date of objectively documented progression criteria or the date of subsequent therapy, whichever occurs first (up to approximately 14 months) | 
| Duration of Response (DOR) | Duration of Response (DOR) is defined as the time between the date of first documented response (complete response (CR) or partial response (PR)) to the date of the first documented progression, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or death due to any cause, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From first dose to the date of the first documented progression or death due to any cause, whichever occurs first (up to approximately 14 months) | 
| Progression Free Survival (PFS) | Progression Free Survival (PFS) is defined as the time between the date of first dose and the first date of documented progression, as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or death due to any cause, whichever occurs first. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, 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 first dose to the first date of documented progression or death due to any cause, whichever occurs first (up to approximately 14 months) | 
| Time to Objective Response (TTR) | Time to Objective Response (TTR) is defined as the time between the date of the first dose and the first confirmed documented response (complete response (CR) or partial response (PR)) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From first dose to the first confirmed documented response (up to approximately 14 months) | 
| The Number of Participants Experiencing Adverse Events (AEs) | The number of participants with any grade adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. | From first dose and 100 days after lost dose (up to approximately 14 months) |