Cabozantinib Plus Nivolumab Is Granted Full Approval for Frontline RCC Indication

The FDA granted approval to the combination use of cabozantinib plus nivolumab ahead of its February PDUFA date as therapy for the first-line treatment of patients with advanced renal cell carcinoma.

The FDA has granted approval to the supplemental biologics license application for the combination of cabozantinib (Cabometyx) and nivolumab (Opdivo) as therapy for patients with advanced renal cell carcinoma (RCC) in the frontline setting, according to Exelixis, the developer of cabozantinib.

This approval follows a priority review designation from the FDA that was granted in October, and comes ahead of the assigned a Prescription Drug User Fee Act (PDUFA) goal date of February 20, 2021.

Efficacy of the combination was verified in the pivotal phase 3 CheckMate 9ER trial (NCT03141177), which compared the combination versus standard-of-care therapy with sunitinib (Sutent) in patients with previously untreated RCC

“This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib–progression-free survival [PFS], overall survival [OS], and objective response rate [ORR]–while showing a low rate of treatment discontinuations due to side effects. The therapeutic benefit demonstrated in CheckMate 9ER and quality-of-life measures explored emphasize the role of this combination for patients with advanced kidney cancer,” Toni Choueiri, MD, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School, said in a press release. “With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer.”

Data from the trial presented at the European Society for Medical Oncology 2020 Virtual Congress demonstrated statistically significant improvement in OS with the experimental combination versus sunitinib, with medians not reached in either arm (HR, 0.60; 98.89% CI, 0.40-0.89; P = .001). The median PFS was also improved, at 16.6 months in the cabozantinib and nivolumab arm versus 8.3 months with sunitinib, and this association was found to be statistically significant (HR, 0.51; 95% CI, 0.41-0.64; P <.0001). ORR was almost doubled in the experimental arm, at 56% versus 27% with sunitinib.

The combination was generally well tolerated and mimicked the known safety profiles of both agents. The most common adverse reactions that were noted in 20% of patients or more in the cabozantinib/nivolumab arm included diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough and upper respiratory tract infection. The discontinuation rate from all causes was around 20%.

“While significant progress has been made in the treatment landscape for advanced kidney cancer over the last several years, patients still need more therapeutic options to treat this disease as we search for a possible cure,” Bryan Lewis, President and Co-founder of KidneyCAN, said in a press release. “As patients are living longer with advanced kidney cancer, focusing on the safety and effectiveness of new treatments has become even more important. The findings for the combination of cabozantinib and nivolumab in the CheckMate 9ER trial make the FDA approval of this combination a notable development for the patient community.”

In total, 651 patients with untreated advanced or metastatic RCC with a clear cell component were randomized to cabozantinib at 4 mg daily plus nivolumab at 240 mg intravenously every 2 weeks (n = 323) or oral sunitinib administered at 50 mg daily on a 4-weeks-on/2-weeks-off cycle (n = 328). PFS was the primary end point with secondary end points of OS, ORR, and safety.

Both nivolumab and cabozantinib are already approved for separate indications in RCC. This combination is currently under review for approval by other global agencies.


Exelixis Announces U.S. FDA approval of Cabometyx (cabozantinib) in Combination with Opdivo (nivolumab) as a First-Line Treatment for Patients with Advanced Renal Cell Carcinoma. News release. January 22, 2021. Accessed January 22, 2021.

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