FDA approves nivolumab and hyaluronidase-nvhy for subcutaneous injection

On December 27, 2024, the Food and Drug Administration approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig, Bristol Myers Squibb Company) for subcutaneous injection across approved adult, solid tumor nivolumab (Opdivo, Bristol Myers Squibb Company) indications as monotherapy, monotherapy maintenance following completion of Opdivo plus Yervoy (ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib.

The approval includes indications 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. Opdivo Qvantig is not indicated in combination with intravenous ipilimumab. The prescribing information provides specific indications and further information for Opdivo Qvantig at Drugs@FDA.

Efficacy and Safety

The subcutaneous injection of nivolumab and hyaluronidase-nvhy was evaluated in CHECKMATE-67T (NCT04810078), a multicenter, randomized, open-label trial in patients with advanced or metastatic clear cell renal cell carcinoma who received no more than 2 prior systemic treatment regimens. A total of 495 patients were randomized 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 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 C_avg over 28 days and C_min 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.

Recommended Dosage

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 Oncology Center of Excellence. 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 (IMoH). 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 or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on X: @FDAOncology.