Nivolumab and Hyaluronidase-nvhy Approved for Subcutaneous Injection
Expert Perspectives · Lyn Brook · 2024-12-31
The FDA has approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig™, Bristol Myers Squibb Company) for subcutaneous injection across approved adult indications of nivolumab (Opdivo®, Bristol Myers Squibb Company) as monotherapy, as monotherapy maintenance after completing nivolumab/ipilimumab combination therapy, or in combination with chemotherapy or cabozantinib.
Approved indications covered by this approval are for 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. Nivolumab and hyaluronidase-nvhy is not indicated in combination with intravenous ipilimumab.
Why Is the Approval Important?
“Intravenous (IV) administration of immune checkpoint inhibitors such as nivolumab carries a level of burden for both patients and healthcare systems due to the chronicity of treatment, long periods of time spent in the clinic for administration, the need for venous access, and, frequently, the use of a permanent access port, which is commonly associated with several complications,” wrote Laurence Albiges, MD, PhD, and colleagues, in their published results of the CheckMate-67T trial (NCT04810078), on which approval was based. “Evolving treatment paradigms require delivery options that reduce the treatment burden for patients while improving the efficiency of healthcare systems. Subcutaneous (SC) administration is typically preferred by patients over infusion and has a shorter preparation and chair occupancy time, which may improve healthcare resource utilization and reduce administrative workload.”
Investigating CheckMate-67T
Efficacy was measured in the phase 3, open-label, multicenter trial which enrolled 495 patients with advanced or metastatic clear cell renal cell carcinoma who had received no more than two prior systemic treatment regimens. Patients were randomized 1:1 to receive either subcutaneous nivolumab and hyaluronidase-nvhy or intravenous nivolumab.
The primary end point was to assess the nivolumab exposure of subcutaneous administration of nivolumab and hyaluronidase-nvhy compared to intravenous nivolumab. A key secondary end point included was the evaluation of overall response rate as assessed by Blinded Independent Central Review (BICR).
The trial met the predefined acceptance margin for pharmacokinetic end points, with the lower boundary of 90% confidence interval of geometric mean ratios of not less than 0.8 for both serum nivolumab Cavg over 28 days and Cmin at steady state. The nivolumab and hyaluronidase-nvhy arm saw an overall response rate of 24% versus 18% in the intravenous nivolumab arm.
Adverse Events
The most common adverse reactions experienced in ≥10% of patients receiving nivolumab and hyaluronidase-nvhy were fatigue, musculoskeletal pain, pruritus, rash, and cough.
Putting It Into Context
“This trial demonstrated that nivolumab SC was noninferior to nivolumab IV,” concluded Dr. Albiges and colleagues. “The safety profile of nivolumab SC was consistent with that of nivolumab IV, with no new safety concerns emerging. These findings support the use of nivolumab SC as a new option to reduce patient treatment burden and improve healthcare efficiency across solid tumors.”
Dosing Instructions
The recommended dosage of nivolumab and hyaluronidase-nvhy depends on the specific indication and is either 600 mg nivolumab and 10,000 units hyaluronidase every two weeks; 900 mg nivolumab and 15,000 units of hyaluronidase every three weeks; or 1,200 mg nivolumab and 20,000 units hyaluronidase every four weeks until disease progression, unacceptable toxicity, or as indicated in the prescribing information.