FDA Approves Subcutaneous Nivolumab Across Existing Solid Tumor Indications

Microscopic photorealistic image of tumor cells - Generated with Adobe Firefly

• The FDA has approved the subcutaneous formulation of nivolumab (Opdivo).
• This approval makes it the first and only subcutaneously administered PD-1 inhibitor.
• Subcutaneous nivolumab is approved in all previously approved solid tumor indications of the intravenous (IV) administration.

On December 27, 2024, subcutaneous nivolumab (Opdivo Qvantig) was approved by the FDA in all previously approved adult solid tumor indications of the agent as monotherapy or monotherapy maintenance or in combination with chemotherapy or cabozantinib (Cabometyx).¹

Subcutaneous nivolumab is formulated with recombinant human hyaluronidase. This approval makes it the first and only subcutaneously administered PD-1 inhibitor.

The subcutaneous formulation is not indicated in combination with intravenous (IV) ipilimumab (Yervoy) but may be given as monotherapy following the completion of ipilimumab. The recommended dosages based on the specific indications are 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, to be given until disease progression, unacceptable toxicity, or as indicated.

Data from the phase 3 CheckMate-67T study (NCT04810078) support this approval. In the trial, investigators sought to evaluate subcutaneous nivolumab vs its IV formulation.²

Findings were presented at the 2024 ASCO Genitourinary Cancers Symposium and showed noninferior pharmacokinetics and response in 495 patients with metastatic clear cell renal cell carcinoma. The overall response rate (ORR) was 24.2% (95% CI, 19.0%-30.0%) with the subcutaneous formulation vs 18.2% (range, 13.6%-23.6%) with the IV formulation, leading to a relative risk ratio of 1.33 (95% CI, 0.94-1.87).

Regarding safety, local injection-site reactions were observed in 8.1% of patients in the subcutaneous nivolumab arm. The reactions were low grade and resolved quickly. Treatment-related serious adverse events were reported in 6.5% of the subcutaneous arm vs 16.5% of the IV arm, and most deaths were attributed to disease progression.

“Intravenous [nivolumab] has helped transform the treatment of several solid tumor types over the past decade, but there remains a need for additional administration options to address treatment burden on patients and improve efficiencies in healthcare systems,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in a press release.³ “We believe this new option, given as a single injection administered in less than 5 minutes, could transform the treatment experience for both patients and physicians.”

REFERENCES:

1. FDA approves nivolumab and hyaluronidase-nvhy for subcutaneous injection. FDA. December 27, 2024. Accessed December 27, 2024. https://tinyurl.com/4yauz6n9

2. George S, Bourlon MT, Chacon MR, et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. J Clin Oncol. 42, LBA360-LBA360(2024). doi:10.1200/JCO.2024.42.4_suppl.LBA360

3. Phase 3 Check-Mate -67T trial of subcutaneous nivolumab (nivolumab and hyaluranidase) meets co-primary end points in advanced or metastatic clear cell renal cell carcinoma. News release. Bristol Myers Squibb. October 19, 2023. Accessed October 15, 2024. https://tinyurl.com/4sryy6vh