On January 22, 2021, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo®) in combination with cabozantinib (Cabometyx®) as first-line treatment for patients with advanced renal cell carcinoma (RCC).

FDA Approves Nivolumab Plus Cabozantinib for Advanced Renal Cell Carcinoma

Efficacy was evaluated in a randomized, open-label trial (CHECKMATE-9ER; NCT03141177) of patients with previously untreated advanced RCC. Patients were randomized to receive either nivolumab 240 mg via IV infusion over 30 minutes every two weeks in combination with cabozantinib 40 mg orally once daily (n = 323) or sunitinib 50 mg orally daily for the first four weeks of a six-week cycle (four weeks on treatment followed by two weeks off) (n = 328).

The trial demonstrated a statistically significant improvement in progression-free survival (PFS), overall survival (OS), and confirmed overall response rate (ORR) for patients treated with nivolumab plus cabozantinib compared to those who received sunitinib. Median PFS per blinded independent central review (BICR) was 16.6 months versus 8.3 months (hazard ratio = 0.51; 95% CI = 0.41, 0.64). Median OS was not reached in either arm (hazard ratio = 0.60; 95% CI = 0.40, 0.89). Confirmed ORR per BICR was 55.7% and 27.1% in the nivolumab plus cabozantinib and sunitinib arms, respectively.

The most common adverse reactions (≥ 20%) were 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.

The recommended dose is nivolumab 240 mg every two weeks via 30-minute IV infusion or 480 mg every four weeks via 30-minute IV infusion in combination with cabozantinib 40 mg orally once daily without food until patients experience disease progression or unacceptable toxicity.

View full prescribing information for nivolumab.
View full prescribing information for cabozantinib.

The nivolumab review used the Real Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application. Both the nivolumab and the cabozantinib applications used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the applications approximately one month ahead of the goal date.

The nivolumab application was granted fast track review, and both the nivolumab and cabozantinib applications were granted priority review. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088. 

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.