FDA Accepts sBLA for Nivolumab Plus Ipilimumab in Intermediate- and Poor-Risk Patients With Advanced Renal Cell Carcinoma

On December 13, the U.S. Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) for priority review of nivolumab (Opdivo) plus ipilimumab (Yervoy) to treat intermediate- and poor-risk patients with advanced renal cell carcinoma. The FDA also previously granted Breakthrough Therapy designation for this application—the second indication for which the combination of nivolumab and ipilimumab has received this designation. 

The application is based on data from the phase III CheckMate-214 study, which was stopped early based on the recommendation of an independent data monitoring committee following a planned interim analysis of overall survival. The results of the study were recently presented by Escudier et al at the European Society for Medical Oncology 2017 Congress (Abstract LBA5).

The application has an action date of April 16, 2018.

About CheckMate-214

CheckMate-214 is a phase III, randomized, open-label study evaluating the combination of nivolumab plus ipilimumab vs sunitinib (Sutent) in patients with previously untreated advanced or metastatic renal cell carcinoma.

Patients in the combination group received nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by ipilimumab at 3 mg/kg every 2 weeks. Patients in the comparator group received sunitinib at 50 mg once daily for 4 weeks, followed by 2 weeks off before continuation of treatment. Patients were treated until progression or unacceptable toxic effects.

The primary endpoints of the trial are overall survival, progression-free survival, and objective response rate in an intermediate- to poor-risk patient population (approximately 75% of patients). Safety is a secondary endpoint. The study met the coprimary endpoints of improved overall survival and objective response rate compared to sunitinib in intermediate- and poor-risk patients. While the combination demonstrated an improvement in progression-free survival relative to sunitinib (another coprimary endpoint), it did not reach statistical significance.

Adverse events leading to treatment discontinuation were reported in 22% of patients (547) in the combination group, compared with 12% of patients in the sunitinib group (535). The most common grade 3/4 adverse events in the combination group were fatigue (4%), diarrhea (4%), rash (2%), nausea (2%), and, in less than 1% each, pruritus, hypothyroidism, vomiting, and hypertension. In the sunitinib group, the most common grade 3/4 adverse events were hypertension (16%), fatigue (9%), palmar-plantar erythrodysesthesia syndrome (9%), stomatitis (3%), mucosal inflammation (3%), vomiting (2%), nausea (1%), decreased appetite (1%), hypothyroidism (< 1%) and dysgeusia (< 1%). There were seven treatment-related deaths in the combination group and four in the sunitinib group.

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®.


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