The Food and Drug Administration (FDA) has accepted for Priority Review the regulatory applications for nivolumab (Opdivo®; Bristol Myers Squibb) and cabozantinib (Cabometyx®; Exelixis) for the combination treatment of advanced renal cell carcinoma (RCC).

The applications are supported by data from the multinational, open-label, randomized phase 3 CheckMate -9ER trial that compared the efficacy and safety of nivolumab, a programmed death receptor-1 blocking antibody, plus cabozantinib, a tyrosine kinase inhibitor, to sunitinib in 651 adults with previously untreated advanced or metastatic RCC. Patients were randomized 1:1 to receive nivolumab plus cabozantinib or sunitinib. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response rate (ORR).

Results showed that treatment with nivolumab plus cabozantinib reduced the risk of death by 40% vs sunitinib (hazard ratio [HR] 0.60; 98.89% CI, 0.40-0.89; P =.0010; median OS was not reached in either arm).  Among patients treated with the combination therapy, median PFS was 16.6 months vs 8.3 months for those who received sunitinib (HR 0.51; 95% CI, 0.41-0.64; P <.0001).

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Additionally, superior ORR and complete response rates (56% and 8%, respectively) were observed with nivolumab plus cabozantinib compared with sunitinib (27% and 5%, respectively). The median duration of response with the combination treatment was 20.2 months vs 11.5 months with sunitinib. Moreover, patients treated with the combination also reported statistically significant improvements in health-related quality of life.

As for safety, nivolumab plus cabozantinib was found to be well tolerated with a low rate of treatment-related discontinuations vs sunitinib (3% vs 9%, respectively). Findings from the study showed that the frequency of treatment-related adverse events was higher with the combination therapy vs sunitinib (97% vs 93% for any grade; 61% vs 51% for grade 3 and higher).

“With their complementary mechanisms of action and evidence that Cabometyx may promote a more immune-permissive environment, we believe there is opportunity for additive or synergistic effects with this potential combination regimen,” said Gisela Schwab, MD, president, product development and medical affairs and chief medical officer, Exelixis.

A Prescription Drug User Fee Act (PDUFA) target date of February 20, 2021 has been set for both applications.

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  1. US Food and Drug Administration accepts for Priority Review applications for Opdivo® (nivolumab) in combination with Cabometyx® (cabozantinib) in advanced renal cell carcinoma. [press release]. Princeton, NJ & Alameda, CA: Bristol Myers Squibb and Exelixis, Inc; October 19, 2020. 
  2. Opdivo® (nivolumab) in combination with Cabometyx® (cabozantinib) demonstrates significant survival benefits in patients with advanced renal cell carcinoma in pivotal phase 3 CheckMate -9ER trial. Princeton, NJ & Alameda, CA: Bristol Myers Squibb and Exelixis, Inc; September 19, 2020.

This article originally appeared on MPR