Nivolumab plus ipilimumab achieves durable responses and has manageable safety in metastatic RCC.
Major finding: Nivolumab plus ipilimumab achieves durable responses and has manageable safety in metastatic RCC.
Concept: In an open-label phase I trial nivolumab plus ipilimumab achieved an overall response rate of 40.4%.
Impact: Combined PD-1 and CTLA4 blockade may be effective in patients with metastatic RCC.
Combination immunotherapy with the anti–PD-1 antibody nivolumab and the anti-CTLA4 antibody ipilimumab has greater antitumor activity than either monotherapy in patients with melanoma or lung cancer. However, this combination has not been tested in patients with metastatic renal cell carcinoma (mRCC), although single-agent therapy with nivolumab or ipilimumab has demonstrated clinical activity in these tumors. In the CheckMate 016 trial, a phase I, open-label, parallel-cohort, dose-escalation study, Hammers and colleagues evaluated the safety and efficacy of nivolumab plus ipilimumab in patients with mRCC. Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1; 47 patients), nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3; 6 patients), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3; 47 patients). The primary endpoints included assessment of the overall safety and tolerability of nivolumab plus ipilimumab. Secondary end points included overall response rate, duration of response, and progression-free survival. The N3I3 patients were not evaluable due to disease progression, treatment-related toxicity, or withdrawal of consent. Serious adverse events were reported in 62.8% of N3I1 and N1I3 patients, and treatment-related adverse events led to discontinuation in 10.6% of N3I1 patients and 27.7% of N1I3 patients. The overall response rate was 40.4%. In the N3I1 arm 5 patients (10.6%) achieved complete responses and 14 patients (29.8%) achieved partial responses. In the N1I3 arm 19 patients (40.4%) experienced partial responses. Responses were rapid and sustained, with ongoing responses observed in 8 patients (42.1%) in the N3I1 arm and 7 patients (36.8%) in the N1I3 arm. Median progression-free survival was 7.7 months in the N3I1 arm and 9.4 months in the N1I3 arm. Collectively, these findings suggest that combination immunotherapy with nivolumab plus ipilimumab has a manageable safety profile and durable antitumor activity in patients with mRCC, supporting further clinical investigation of the N3I1 regimen, which had a more favorable safety profile.