The FDA has granted priority review status to a supplemental New Drug Application for nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) for the treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC).

The application is based on data from the phase 3, randomized, open-label CheckMate-214 trial, which was halted early because of a recommendation from an independent Data Monitoring Committee after a planned interim analysis of overall survival (OS).

CheckMate-214 is evaluating the combination of nivolumab and ipilimumab versus sunitinib (Sutent, Pfizer) in 1,096 patients with previously untreated advanced or metastatic RCC. Results from the study were recently presented at the European Society for Medical Oncology 2017 Congress by Bernard Escudier, from the Institut Gustave Roussy, in Villejuif, France (abstract LBA5). (See related story, goo.gl/CA57DJ). In the combination group, 550 patients received 3 mg/kg of nivolumab and 1 mg/kg of ipilimumab every three weeks for four doses, followed by 3 mg/kg of nivolumab every two weeks. In the sunitinib group, 546 patients received 50 mg of sunitinib once daily for four weeks, followed by two weeks off before continuation of treatment. In both groups, patients were treated until disease progression or unacceptable toxicity.  

The primary end points of the trial are OS, progression-free survival and objective response rate in intermediate- to poor-risk patients (approximately 75% of patients), and safety is a secondary end point. The study met the coprimary end points of improved OS and objective response rate compared with sunitinib in intermediate- and poor-risk patients. The combination therapy improved OS in the intermediate-/poor-risk group, with the median OS not reached in the combination group, versus 26 months in the sunitinib group (hazard ratio, 0.63; P<0.0001). The combination also improved progression-free survival relative to sunitinib, but the result was not statistically significant.

Adverse events (AEs) leading to discontinuation were reported in 22% of patients (n=547) in the combination group and 12% of those (n=535) in the sunitinib group. The most common grade 3/4 AEs in the combination group were fatigue (4%), diarrhea (4%), rash (2%), nausea (2%), pruritus (<1%), hypothyroidism (<1%), vomiting (<1%) and hypertension (<1%). The most common grade 3/4 AEs in the sunitinib group 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.

“At BMS, we hope to provide treatment options to patients with advanced forms of renal cell carcinoma,” said Murdo Gordon, Bristol-Myers Squibb’s executive vice president and chief commercial officer. He called the FDA decision “an important step in our ongoing efforts to advance therapies to address a high unmet need in first-line treatment of kidney cancer in intermediate- and poor-risk patients.”

The FDA previously granted breakthrough therapy designation for this application. The application has an action date of April 16, 2018.

—Clinical Oncology News Staff