FDA Approves Nivolumab Plus Cabozantinib in Advanced Renal Cell Carcinoma

The FDA has granted approval to the combination of nivolumab and cabozantinib as treatment of advanced renal cell carcinoma in the frontline setting.

The FDA has granted approval to the combination of nivolumab (Opdivo) and cabozantinib (Cabometyx) as treatment of advanced renal cell carcinoma in the frontline setting, announced the FDA, in a press release.1

Approval of the supplemental Biologics License Application for the combination was supported by results from the phase 3 CheckMate 9ER clinical trial (NCT03141177), in which nivolumab/cabozantinib demonstrated statistically significant improvements in progression-free survival (PFS), overall survival (OS) and good confirmed overall response rate (ORR).

“This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib; progression-free survival, overall survival and objective response rate, 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,” said 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, in a statement.2 “With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer.”

In the study, 651 patients with advanced RCC were randomized 1:1 to receive either the frontline combination of nivolumab plus cabozantinib (n = 323) or sunitinib (n = 328). Nivolumab was administered by intravenous infusion at 240 mg every 2 weeks, and cabozantinib was given orally at 40 mg daily. In the control arms, sunitinib was administered orally at a dose level of 50 mg daily on a cycle of 4-weeks-on and 2-weeks-off. All study treatments were continued until disease progression or unacceptable toxicity.

According to the blinded independent central review committee, the median PFS observed with nivolumab plus cabozantinib was 16.6 months compared with 8.3 months in the sunitinib arm, (HR, 0.51; 95% CI, 0.41-0.64), at a median follow-up of 18.1 months. The median OS was not yet reached in either arm of the study (HR, 0.60; 95% CI, 0.40-0.89).3

In terms of response, patients treated with nivolumab plus cabozantinib achieved a 55.7% ORR compared with 27.1% in the sunitinib arm. Responses in the combination arm included complete responses (CRs) in 8.0% of patients and partial responses (PRs) in 47.7%. In the sunitinib arm, only 4.6% of patients had CRs and 22.6% had PRs.

Adverse events (AEs) observed in the study subjects led to treatment discontinuation in 50%. The most common AEs (≥20%) included diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia syndrome, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

Treatment-related AEs (TRAEs) were also seen in the study and led to discontinuation of treatment in 15.3% of the nivolumab/cabozantinib arm versus 8.8% of the sunitinib arm. Overall, the most common TRAEs were similar between patients treated with the combination and those treated with sunitinib monotherapy.

Based on the safety data from CheckMate 9ER, the recommended dose is nivolumab 240 mg given every 2 weeks by 30-minute IV. Nivolumab can also be administered at a 480-mg dose every 4 weeks by 30-minute IV in combination with cabozantinib 40 mg given orally once daily without food. Treatment should continue until disease progression or unacceptable toxicity.


1. FDA approves nivolumab plus cabozantinib for advanced renal cell carcinoma. News release. FDA. January 22, 2021. Accessed January 22, 2021. https://bit.ly/3iEIlMj

2. 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. New release. Exelixis. January 22, 2021. Accessed January 22, 2021. https://bit.ly/2Npuu0J

3. Choueiri TK, Powles T, Burotto M, et al. Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. Ann Oncol. 2020;31(4). Abstract 696O.