Bristol Myers Squibb and Exelixis said Monday that a Phase III study investigating the combination of Opdivo (nivolumab) and Cabometyx (cabozantinib) in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC) met its primary endpoint of progression-free survival (PFS) at final analysis. The companies noted that the CheckMate -9ER trial also achieved the secondary goals of overall survival (OS) at a pre-specified interim analysis and objective response rate.
In the study, patients with previously untreated advanced or metastatic RCC were randomised to receive the combination of Opdivo and Cabometyx or Pfizer's Sutent (sunitinib) alone. The companies noted that the primary efficacy analysis compared the doublet combination versus Sutent in all randomised patients, with a median follow-up of 18.1 months.
Top-line results showed that the combination of Opdivo and Cabometyx significantly reduced the risk of disease progression or death compared with Sutent, with a hazard ratio of 0.51. Meanhwhile, for OS, the hazard ratio was 0.60, while the combination was associated with "deep and durable" responses. Bristol Myers Squibb and Exelixis indicated that Opdivo and Cabometyx demonstrated a favourable safety profile, with a low frequency of treatment discontinuations due to adverse events.
"Given the growing body of data showing that Cabometyx may create a more immune-permissive tumour environment that may enhance response to immune checkpoint inhibitors, we have been eagerly awaiting the results," remarked Gisela Schwab, chief medical officer at Exelixis, whose shares jumped as much as 23% on the news. Meanwhile, Brian Lamon, Bristol Myers Squibb's development lead for genitourinary cancers, said "we look forward to working with global health authorities to help bring this new combination regimen to previously untreated patients."
In RCC, Opdivo is currently approved for use in patients with advanced disease who have received prior anti-angiogenic therapy, while the PD-1 immune checkpoint inhibitor is also authorised in combination with Bristol Myers Squibb's Yervoy (ipilimumab) for the treatment of patients with intermediate- or poor-risk, previously untreated disease. Meanwhile, the tyrosine kinase inhibitor Cabometyx is indicated for the treatment of patients with advanced RCC. Ipsen holds rights to the drug outside of the US and Japan, with Takeda holding rights in the latter market.
Last year, the FDA authorised Merck & Co.'s Keytruda (pembrolizumab) in combination with Pfizer's tyrosine kinase inhibitor Inlyta (axitinib) as a first-line treatment for patients with advanced RCC. The approval was supported by findings from the Phase III KEYNOTE-426 trial, with results showing that the combination cut the risk of death by 47% versus Sutent monotherapy, while the risk of disease progression or death was reduced by 31%.
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