FDA Approval Sought for Frontline Cabozantinib/Nivolumab Combo in Advanced RCC


A supplemental new drug application has been submitted to the FDA for the combination of cabozantinib and nivolumab as a treatment for patients with advanced renal cell carcinoma.

Gisela Schwab, MD

A supplemental new drug application has been submitted to the FDA for the combination of cabozantinib (Cabometyx) and nivolumab (Opdivo) as a treatment for patients with advanced renal cell carcinoma (RCC), according to an announcement by Exelixis, the developer of cabozantinib.1

The application is based on findings from the phase 3 CheckMate-9ER trial, which is evaluating the combination versus sunitinib in patients with previously untreated advanced or metastatic RCC. In April 2020, Exelixis and Bristol Myers Squibb, the manufacturer of nivolumab, announced that the study had met its primary end point of progression-free survival (PFS) at the final analysis. The full findings will be presented during the 2020 ESMO Virtual Congress in September.

“We are excited to complete our first regulatory submission for Cabometyx in combination with an immune-checkpoint inhibitor based on the positive results from the CheckMate-9ER phase 3 pivotal trial, which showed a statistically significant and clinically meaningful benefit in the key efficacy measures of progression-free survival, overall survival, and objective response rate for patients with previously untreated kidney cancer,” Gisela Schwab, MD, president of Product Development and Medical Affairs, and chief medical officer of Exelixis, stated in a press release.

In the open-label, international, phase 3 CheckMate-9ER trial (NCT03141177), investigators randomized an estimated 638 patients with advanced or metastatic RCC 1:1 to receive frontline nivolumab/cabozantinib or sunitinib.

Beyond the primary PFS end point, secondary end points include overall survival at a prespecified interim analysis and objective response rate, as well as safety.

To be eligible for enrollment, patients must have had histological confirmation of advanced or metastatic RCC with a clear-cell component, and can include those with sarcomatoid features. Patients could not have prior systemic therapy except for 1 prior adjuvant or neoadjuvant treatment for resectable disease. Additionally, those with active central nervous system metastases, active or suspected autoimmune disease, requiring treatment with corticosteroids, and have received a live/attenuated vaccine within 30 days of first study treatment were excluded from enrollment.

In a preliminary assessment, it was reported that the regimen showed a favorable safety profile, along with a low frequency of treatment discontinuations due to adverse effects.

“We expect that, if approved, the combination of Cabometyx and Opdivo will be an important new first-line treatment regimen for RCC patients who need additional therapeutic options that extend survival,” Schwab concluded in the press release. “We look forward to continuing to work closely with Bristol Myers Squibb and the FDA through the regulatory review process.”

The FDA approved cabozantinib in December 2017 for previously untreated patients with advanced RCC, based on a meaningful improvement in PFS versus sunitinib in the CABOSUN trial.2 Nivolumab was approved by the FDA in November 2015 as a treatment for patients with metastatic RCC following prior antiangiogenic therapy, which was based on an extension in OS in the CheckMate-025 trial.3 In the frontline setting, the FDA approved nivolumab in April 2018 for use in combination with ipilimumab as a frontline treatment for intermediate- and poor-risk patients with advanced RCC.


  1. Exelixis announces submission of supplemental new drug application to U.S. Food and Drug Administration for Cabometyx (cabozantinib) in combination with Opdivo (nivolumab) for advanced renal cell carcinoma. News release. Published August 24, 2020. Accessed August 24, 2020. https://bit.ly/32iRdzv.
  2. Choueiri TK, Hessel C, Halabi S, et al. Progression-free survival (PFS) by independent review and updated overall survival (OS) results from Alliance A031203 trial (CABOSUN): Cabozantinib versus sunitinib as initial targeted therapy doe patients (pts) with metastatic renal cell carcinoma (mRCC). In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract LBA38.
  3. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803-1813. doi:10.1056/NEJMoa1510665
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