FDA Accepts Supplemental New Drug Application for Nivolumab/Cabozantinib Combination for Advanced Renal Cell Carcinoma

The FDA announced it has accepted a supplemental Biologics License Application (sBLA) and supplemental New Drug Application (sNDA) for nivolumab (Opdivo) in combination with cabozantinib (Cabometyx) for patients with advanced renal cell carcinoma (RCC).

The FDA action was based on results from the Phase 3 CheckMate -9ER trial evaluating nivolumab in combination with cabozantinib compared with sunitinib among patients with previously untreated advanced RCC. The results showed that the combination demonstrated significant improvements across all efficacy endpoints, including overall survival, progression-free survival, and objective response rate compared with sunitinib, according to a Bristol Myers Squibb press release.

“We have witnessed practice-changing advancements in the treatment of renal cell carcinoma in recent years, but we recognize the importance of providing patients and physicians with additional options that can help them take control of the disease,” said Mark Rutstein, vice president and development program lead, Opdivo, Bristol Myers Squibb, in the press release. “In the CheckMate -9ER trial, combining Opdivo and Cabometyx, two proven agents with strong clinical legacies in advanced renal cell carcinoma, led to superior efficacy across all endpoints. We look forward to working with the FDA to bring this potential treatment option to physicians and their patients who choose an immunotherapy plus tyrosine kinase inhibitor regimen.”

In the open-label, randomized, multi-national, phase 3 CheckMate -9ER trial, 651 patients with untreated advanced or metastatic RCC have been randomized to receive nivolumab in combination with cabozantinib (n=323) or sunitinib (n=328). The primary efficacy analysis is comparing the doublet combination compared with sunitinib in all randomized patients.

The combination was found to be well-tolerated, with a low rate of treatment-related discontinuations and showed the known safety profiles of the immunotherapy and tyrosine kinase inhibitor components among patients with previously untreated advanced RCC.

Further, patient-reported outcomes data showed that nivolumab in combination with cabozantinib was associated with statistically significant improvements in health-related quality of life at most time points compared with sunitinib, according to a press release.

The FDA previously granted the combination with Priority Review and assigned a PDUFA goal date of February 20, 2021.

“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. “Based on strong supporting data from CheckMate -9ER, the acceptance of our application is important progress in our efforts to make Cabometyx in combination with Opdivo available to patients with advanced kidney cancer who need additional treatment options. We look forward to working with the FDA throughout the ongoing review process.”