Phase 3 CheckMate-9ER trial showed that Opdivo plus Cabometyx improved overall survival, progression-free survival and objective response rate

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Entrance to the Bristol-Myers Squibb building in New Jersey. (Credit: Jonathan Schilling/Wikipedia.)

The US Food and Drug Administration (FDA) has granted priority review for Opdivo (nivolumab) in combination with Cabometyx (cabozantinib) to treat advanced renal cell carcinoma (RCC).

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor, developed by Bristol-Myers Squibb to harness the body’s own immune system to restore anti-tumour immune response.

Cabometyx is an approved medication developed by Exelixis, for the treatment of advanced RCC and HCC in patients who have been previously treated with sorafenib.

FDA has accepted Bristol-Myers’ supplemental Biologics License Application (sBLA) for Opdivo, and Exelixis’ supplemental New Drug Application (sNDA) for Cabometyx.

The US regulatory agency has granted Priority Review to both applications and finalised 20th February, 2021 as Prescription Drug User Fee Act (PDUFA) goal date, or target action date.

Bristol-Myers Squibb vice-president, OPDIVO development program lead Mark Rutstein said: “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.

“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.”

Opdivo plus Cabometyx superior to sunitinib in Phase 3 CheckMate-9ER trial

The regulatory filings were based on results from the Phase 3 CheckMate-9ER, an open-label, randomised, multi-national trial, which evaluated Opdivo plus Cabometyx in patients with previously untreated advanced or metastatic RCC, compared to sunitinib.

The clinical trial was conducted by Bristol-Myers Squibb and Ono Pharmaceutical, and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical.

In the Phase 3 CheckMate-9ER trial, the enrolled 651 subjects were randomised to either receive Opdivo plus Cabometyx therapy or sunitinib alone.

Progression-free survival (PFS) was the primary endpoint, while overall survival (OS) and objective response rate (ORR) were the secondary endpoints.

In the study, the drug combination has improved all efficacy endpoints, including overall survival (OS), progression-free survival (PFS) and objective response rate (ORR).

Also, the drug combination was well tolerated, with minimised treatment-related discontinuations, and demonstrated the known safety profiles of the medication in patients with previously untreated advanced RCC.

Exelixis president, product development and medical affairs and chief medical officer Gisela Schwab said: “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.

“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.”