FDA Approves Subcutaneous Nivolumab and Hyaluronidase-nvhy

On December 27, 2024, the Food and Drug Administration (FDA) announced the approval of a new subcutaneous formulation of nivolumab and hyaluronidase-nvhy, marketed as Opdivo Qvantig by Bristol Myers Squibb. This new method of administration is approved for various adult solid tumor indications where nivolumab (Opdivo) is used as a standalone therapy, as maintenance therapy following a combination treatment with Opdivo and Yervoy (ipilimumab), or alongside chemotherapy or cabozantinib. The approved indications include several types of cancer: 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. However, Opdivo Qvantig is not approved for use in combination with intravenous ipilimumab.

The efficacy and safety profile of the subcutaneous injection was evaluated in the CHECKMATE-67T trial, a multicenter, randomized, open-label study focused on patients with advanced or metastatic clear cell renal cell carcinoma. Participants in the trial had previously undergone no more than two systemic treatment regimens. A total of 495 patients were involved, receiving either the subcutaneous combination of nivolumab and hyaluronidase-nvhy or intravenous nivolumab.

The primary goal of the CHECKMATE-67T trial was to compare nivolumab exposure from the subcutaneous administration of Opdivo Qvantig with that from the intravenous administration. A key secondary goal was to determine the overall response rate (ORR), which was assessed through a blinded independent central review. The study achieved its pharmacokinetic objectives, with the lower limit of the 90% confidence interval for the geometric mean ratios being above 0.8 for both average serum nivolumab concentration over 28 days and minimum concentration at steady state. The ORR was found to be 24% in the group receiving the subcutaneous formulation, compared to 18% in the intravenous group.

Safety profiles for both the subcutaneous and intravenous forms of nivolumab were similar, with fatigue, musculoskeletal pain, pruritus, rash, and cough being the most frequently reported adverse reactions, occurring in 10% or more of the patients.

The recommended dosing for Opdivo Qvantig varies by indication and is either 600 mg of nivolumab with 10,000 units of hyaluronidase every two weeks, 900 mg of nivolumab with 15,000 units of hyaluronidase every three weeks, or 1,200 mg of nivolumab with 20,000 units of hyaluronidase every four weeks. Treatment continues until disease progression, unacceptable toxicity, or as per prescribing guidelines.

This approval process was conducted as part of Project Orbis, an initiative by the FDA's Oncology Center of Excellence, designed to allow for simultaneous submission and review of oncology drugs across international partners. For this particular review, the FDA collaborated with regulatory bodies in Canada and Israel. The evaluation process is still ongoing in these other jurisdictions.

The review made use of an Assessment Aid, a voluntary submission from the applicant aimed at facilitating the FDA's evaluation. Healthcare professionals are encouraged to report severe adverse events suspected to be related to any medication or device to the FDA's MedWatch Reporting System.