FDA Grants Priority Review to Opdivo-Cabometyx Combo for Advanced Kidney Cancer

The Food and Drug Administration (FDA) recently granted priority review designations to the supplemental biologics license application and supplemental new drug application for Opdivo (nivolumab) in combination with Cabometyx (cabozantinib) for the treatment of patients with advanced renal cell carcinoma, according to the manufacturers of both agents, Bristol Myers Squibb and Exelixis.

“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 Dr. Gisela Schwab, Exelixis’s chief medical officer, in a press release. “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.”

Both filings were based on results from the open-label, randomized, multi-national phase 3 CheckMate -9ER trial (NCT03141177) – designed to evaluate Opdivo in combination with Cabometyx (323 patients), compared with Sutent (sunitinib; 328 patients), in 651 patients with previously untreated advanced RCC.

Measuring progression-free survival (PFS), or the time a patient’s cancer does not progress during or after treatment, was the main goal of the study. Secondary end points included overall survival (OS) and objective response rate (ORR). Moreover, patient-reported outcomes data showed statistically significant improvements in health-related quality of life at most time points.

Median PFS was doubled with the combination regimen, compared with Sutent (16.6 months vs. 8.3 months). In addition, the combination reduced the risk for death by 40%; however, median OS was not reached in either arm.

Patients who received the combination (56%) were twice as likely to respond to the treatment compared to those who received Sutent (27%). In addition, 8% vs. 5%, respectively, achieved a complete response. Lastly, Opdivo plus Cabometyx induced a longer duration of response, compared with Sutent (median, 20.2 months vs. 11.5 months).

Patients appeared to tolerate the combination well and the results were consistent with known safety profiles of both agents, with a low rate of treatment-related discontinuations. Most of the participants in the combination (97%) and Sutent (93%) arm reported experiencing a treatment-related adverse event.

Neither the combination (3%) arm nor the Sutent (9%) arm reported a significant number of treatment-related discontinuations.

“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 of Opdivo, in the 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 end points. 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.”

The agency is set to make its decision on whether to approve the drug for this use by Feb. 20, 2021.

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