Phase II Study of Optimized Management of Nivolumab Based on Response in Patients with Advanced Renal Cell Carcinoma (OMNIVORE Study)

Status: 
Recruiting
Sponsor: 
Dana-Farber Cancer Institute
Enrollment: 
58
Study Design: 
This Phase II, open-label study enrolls patients with treatment-naïve or previously treated aRCC with either clear cell or non-clear cell disease. Prior immune checkpoint inhibitor therapy is not permitted. All patients enrolled receive nivolumab every 2 weeks initially, with subsequent management outlined based on RECIST response within the first 6 months of nivolumab. If patients have a confirmed partial response (PR) or complete response (CR), nivolumab will be discontinued and patients will be observed. At the time of progression, these patients will be treated again with nivolumab, and if there is further progression, 2 treatments with ipilimumab every 3 weeks will be given in addition to nivolumab (which will be given every 3 weeks when combined with ipilimumab). These patients will be considered part of ‘Arm A.’ If, instead, patients are found to have stable disease (SD) or progression (PD) after initial nivolumab treatment, 2 treatments with ipilimumab every 3 weeks will be given while continuing nivolumab, with these patients constituting ‘Arm B.’
Rationale: 
Nivolumab is an established therapy for treatment of advanced RCC (aRCC) after progression on antiangiogenic therapy after the findings of the CheckMate-025 study. The CheckMate-214 trial established the efficacy of nivolumab combined with ipilimumab in intermediate- to poor-risk metastatic RCC but with the tradeoff of increased toxicity as compared to single agent immune checkpoint inhibition. There are also no studies which have addressed the optimal duration of this type of therapy in mRCC, and it is not known if the benefit of combining nivolumab with ipilimumab is derived from combined treatment upfront, if these drugs can be sequenced, or if ipilimumab can convert a non-responder to nivolumab to a responder.
Endpoints: 
There are co-primary endpoints in this trial – the proportion of patients with durable CR/PR at 1 year after nivolumab discontinuation in Arm A and proportion of patients with SD or PD who convert to CR/PR at 1-year after addition of ipilimumab to nivolumab (Arm B). Progression-free survival (PFS), OS, salvage therapy-free interval, safety and immune related objective response rate (irORR) will also be determined as secondary endpoints.
Comments: 
The findings of this Phase II study will help to guide the design of future trials evaluating immune checkpoint inhibitor therapy. For example, if Arm A indicates that a favorable proportion of patients have a durable CR/PR after discontinuation of nivolumab, this would warrant a more robust trial to determine the optimal duration of nivolumab. If Arm B of this trial finds that a promising proportion of patients convert to CR/PR after the addition of ipilimumab, this could indicate that we may be able to spare some patients from the toxicity of combined immunotherapy without sacrificing efficacy.