On 27 December 2024, the US Food and Drug Administration (FDA) approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig, Bristol Myers Squibb Company) for subcutaneous injection across approved adult, solid tumour nivolumab (Opdivo, Bristol Myers Squibb Company) indications as monotherapy, monotherapy maintenance following completion of Opdivo plus ipilimumab (Yervoy) 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, oesophageal carcinoma, gastric cancer, gastro-oesophageal junction cancer, and oesophageal adenocarcinoma. Opdivo Qvantig is not indicated in combination with intravenous ipilimumab.
The subcutaneous injection of nivolumab and hyaluronidase-nvhy was evaluated in CHECKMATE-67T (NCT04810078), a multicentre, randomised, open-label study conducted in patients with advanced or metastatic clear cell RCC who received no more than 2 prior systemic treatment regimens. A total of 495 patients were randomised to receive either subcutaneous nivolumab and hyaluronidase-nvhy or intravenous nivolumab.
The primary objective was to assess the nivolumab exposure of subcutaneous administration of Opdivo Qvantig compared to intravenous nivolumab. The key secondary objective was to evaluate overall response rate (ORR), assessed by blinded independent central review. The study met the predefined acceptance margin for pharmacokinetic endpoints, with the lower boundary of 90% confidence interval [CI] of geometric mean ratios of not less than 0.8 for both serum nivolumab Cavg over 28 days and Cmin at steady state. ORR was 24% (95% CI 19,30) in the subcutaneous nivolumab and hyaluronidase-nvhy arm and 18% (95% CI 14, 24) in the intravenous nivolumab arm.
In general, CHECKMATE-67T showed a similar safety profile between Opdivo Qvantig and intravenous nivolumab. The most common adverse reactions (≥10%) were fatigue, musculoskeletal pain, pruritus, rash, and cough.
The recommended dosage depends on the specific indication and is either 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 indicated in the prescribing information.
This review was conducted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada and Israel’s Ministry of Health. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
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.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate.