On Dec. 27, the U.S. Food and Drug Administration (FDA) approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig) for subcutaneous injection across previously approved adult, solid tumor nivolumab indications as a monotherapy, as a maintenance therapy after completing nivolumab plus ipilimumab (Yervoy) treatment, or in combination with chemotherapy or cabozantinib.
Subcutaneous injection cuts administration time to 3–5 minutes compared with 30 minutes for intravenous (IV) nivolumab, according to manufacturer Bristol Myers Squibb’s news release. The injection version of the drug, a programmed cell death 1 (PD-1) inhibitor, will be available in early January, Reuters reports.
Nivolumab’s subcutaneous administration is now approved for indications that include renal cell carcinoma, melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma, esophageal carcinoma, gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. The injection is not to be used in combination with ipilimumab for the treatment of renal cell carcinoma.
“This approval of subcutaneous nivolumab gives our patients a new option that can deliver consistent efficacy and comparable safety expected from IV nivolumab, and offers a patient-centric treatment experience,” said Saby George, MD, FACP, a medical oncologist and director of network clinical trials at Roswell Park Comprehensive Cancer Center in Buffalo, New York, in the company’s news release. Dr. George also stated that the drug “may allow patients, in consultation with their doctors, to choose another treatment method and the flexibility to receive treatment closer to home.”
The approval is based on results from the phase 3 randomized, open-label, multicenter, CheckMate-67T trial, which demonstrated consistent efficacy and safety comparable with IV nivolumab. The study included 495 patients who had advanced or metastatic clear cell renal cell carcinoma and had received no more than two systemic treatment regimens. They were randomly assigned to receive either subcutaneous or IV nivolumab. The primary objective was to assess the nivolumab exposure associated with the subcutaneous and IV formulations.
In the trial, subcutaneous nivolumab showed noninferiority to IV nivolumab in the coprimary endpoints of time-averaged concentration over the course of 28 days (Cavg28) and minimum concentration at steady state (Cminss). The geometric mean ratio (GMR) for Cavg28 was 2.10 (90% confidence interval [CI], 2.00–2.20), and the GMR for Cminss was 1.77 (90% CI, 1.63–1.93). Overall response rate (ORR) was the key secondary endpoint. In the injection group, the ORR was 24% (95% CI, 19%–30%) compared with 18% (95% CI, 14%–24%) in the IV group.
The most common adverse reactions, experienced by at least 10% of patients, included fatigue, musculoskeletal pain, pruritus, rash, and cough.
Recommended dosing varies depending on the indication and is 600 mg nivolumab and 10,000 units hyaluronidase every 2 weeks; 900 mg nivolumab and 15,000 units of hyaluronidase every 3 weeks; or 1,200 mg nivolumab and 20,000 units hyaluronidase every 4 weeks until disease progression, unacceptable toxicity, or as prescribing information directs, the FDA states.
BMS states that this is the first subcutaneously administered PD-1 inhibitor to be approved by the FDA.
