On December 27, 2024, the U.S. Food and Drug Administration approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig) for subcutaneous injection across approved adult, solid tumor nivolumab indications as monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab combination therapy, or in combination with chemotherapy or cabozantinib.
The approval includes indications for renal cell carcinoma (RCC), 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. Subcutaneous nivolumab plus hyaluronidase is not indicated in combination with intravenous ipilimumab.
Efficacy and Safety
The subcutaneous injection of nivolumab plus hyaluronidase was evaluated in CheckMate-67T (ClinicalTrials.gov identifier NCT04810078), a multicenter, randomized, open-label trial in patients with advanced or metastatic clear cell RCC who received no more than two prior systemic treatment regimens. A total of 495 patients were randomly assigned to receive either subcutaneous nivolumab plus hyaluronidase or intravenous nivolumab.
The primary objective was to assess the nivolumab exposure of subcutaneous administration of nivolumab plus hyaluronidase compared to intravenous nivolumab. The key secondary objective was to evaluate overall response rate, assessed by blinded independent central review. The trial met the predefined acceptance margin for pharmacokinetic endpoints, 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. Overall response rate was 24% (95% confidence interval [CI] = 19–30) in the subcutaneous nivolumab plus hyaluronidase arm and 18% (95% CI = 14–24) in the intravenous nivolumab arm.
In general, CheckMate-67T showed a similar safety profile between subcutaneous nivolumab plus hyaluronidase and intravenous nivolumab. The most common adverse reactions (≥ 10%) were fatigue, musculoskeletal pain, pruritus, rash, and cough.
Recommended Dosage
The recommended dosage depends on the specific indication and is either nivolumab at 600 mg and hyaluronidase at 10,000 units every 2 weeks; nivolumab at 900 mg and hyaluronidase at 15,000 units every 3 weeks; or nivolumab 1,200 mg and hyaluronidase at 20,000 units every 4 weeks until disease progression, unacceptable toxicity, or as indicated in the prescribing information. For more information regarding specific indications and dosing information, view the full prescribing information.
