Nivolumab Plus Ipilimumab in Metastatic Renal Cell Carcinoma
The phase I CheckMate 016 trial has shown activity of the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) in metastatic renal cell carcinoma. These findings were reported in the Journal of Clinical Oncology by Hammers et al.
Study Details
In the dose-escalation study, patients were randomized to three nivolumab/ipilimumab combination groups and two nivolumab plus tyrosine kinase inhibitor groups. The current report is confined to the nivolumab/ipilimumab groups.
Patients received nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg (N3I1 group, n = 47), nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg (N1I3 group, n = 47), or nivolumab at 3 mg/kg plus ipilimumab at 3 mg/kg (N3I3 group, n = 6) every 3 weeks for 4 doses followed by nivolumab monotherapy at 3 mg/kg every 2 weeks until disease progression or dose-limiting toxicity. All six patients in the N3I3 arm (n = 6) were censored at the time of analysis due to dose-limiting toxicity or other reasons. Overall, 53% and 45% of the N3I1 and N1I3 patients were treatment-naive, respectively.
Combination Activity
At a median follow-up of 22.3 months, confirmed objective response was observed in 40.4% of both groups, with responses ongoing at last analysis in 42.1% of the responders in the N3I1 group and 36.1% in the N1I3 group. Response rates for previously treated and treatment-naive patients were 45.5% and 36.0% in the N3I1 group and 38.5% and 42.9% in the N1I3 group. Progression-free survival at 1 year was 40.0% and 46.4%. Overall survival at 2 years was 67.3% and 69.6%.
Adverse Events
Grade 3 or 4 treatment-related adverse events were reported in 38% of the N3I1 group and in 62% of the N1I3 group. The most common events were increased lipase (15%) in the N3I1 group and increased lipase (28%), increased alanine transaminase (21%), diarrhea (15%), colitis (15%), and increased aspartate transaminase (13%) in the N1I3 group.
The investigators concluded: “Nivolumab plus ipilimumab therapy demonstrated manageable safety, notable antitumor activity, and durable responses with promising [overall survival] in patients with [metastatic renal cell carcinoma].”
The study was supported by Bristol-Myers Squibb.
Hans J. Hammers, MD, PhD, of The University of Texas Southwestern Medical Center, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
