The purpose of this study was to determine the safety, efficacy and optimal dose of Nivolumab in combination with Sunitinib, Pazopanib, or Ipilimumab for the treatment of metastatic renal cell carcinoma (mRCC). Patients in the immune combination arm were randomly assigned to one of three dosing options: nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3).
This is an open-label, dose-escalation, phase I study that investigates for the first time, the efficacy and safety of immune combination therapy PD-1 inhibitor nivolumab and CTLA-4 inhibitor ipilimumab and nivolumab in combination with a tyrosine kinase inhibitor (TKI) in mRCC.
Primary Endpoints: Safety and tolerability of Nivolumab plus TKI or Nivolumab + Ipilimumab measured by the incidence of adverse events, serious adverse events and laboratory abnormalities. Secondary Outcome Measures: Efficacy of Nivolumab plus TKI, or Ipilimumab measured by Objective Response Rate and duration of response according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Safety and efficacy results from the immune combination nivolumab plus ipilimumab arms of the study were recently published (Hammers et al.). Patients in the N3I3 arm were censored due to dose-limiting toxicities. Forty-seven patients were treated in the remaining two immune combination arms. Almost 40% in the N3I1 arm and approximately 60% of the N1I3 arm patients presented grade 3 to 4, treatment-related adverse events. The objective response rate was 40%, with a 2-year overall survival of approximately 70% in both treatment arms.
This study showed that immune combination treatments in mRCC are safe and present promsing efficacy with durable responses in patients. A Phase III study of Nivolumab combined with Ipilimumab versus Sunitinib monotherapy is currently (NCT02231749).