FDA Accepts Nivolumab Subcutaneous Injection Application, With Potential to Boost Access to PD-1 Inhibitors

FDA has accepted Bristol Myer Squibb’s biologics license application (BLA) for its subcutaneous (SC) formulation of the nivolumab, which company officials say has the “potential” to be the first PD-1 inhibitor administered by subcutaneous injection if approved by its target action date of February 28, 2025.¹

Sold as Opdivo, the therapy is formulated with hyaluronidase to create subcutaneous (SC) nivolumab. According to a BMS statement, the BLA covers all previously approved indications for use of intravenous (IV) nivolumab as a monotherapy in adult solid tumors, and all approvals for monotherapy as a maintenance therapy following use of the combination nivolumab plus ipilimumab (Yervoy) or combinations with chemotherapy or cabozantinib (Cabometyx).

Although some warn it’s too soon to say whether the shift to SC nivolumab will be a game-changer, leaders from BMS are enthusiastic about the BLA.

Gina Fusaro, PhD | Image credit: LinkedIn

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” Gina Fusaro, PhD, vice president, global program lead, BMS, said in the statement. “[Nivolumab] is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority.¹

“If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV [nivolumab] but with the improved convenience of an injection administered in 3-5 minutes rather than a 30-to-60-minute infusion.”¹

The BLA is based on results from CheckMate-67T (NCT04810078), a phase 3 randomized trial that compared SC nivolumab and IV nivolumab in patients with advanced or metastatic clear cell renal cell carcinoma who had received prior systemic therapy. A total of 495 patients were evaluated. Coprimary endpoints are time-averaged serum concentration over 28 days and trough serum concentration at steady-state of SC nivolumab vs IV nivolumab. A key secondary endpoint is objective response rate (ORR).

Results were presented earlier this year at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), where data showed the study met both coprimary pharmacokinetic endpoints and its secondary endpoint of ORR, with response rates of 24.2% (95% CI, 19.0%-30.0%) for subcutaneous nivolumab vs 18.2% (95% CI, 13.6%-23.6%) for IV nivolumab.²

A key advantage of subcutaneous nivolumab, and this administration route generally, is the rapid time to give patients the drug. It only takes an average of 5 minutes to administer subcutaneous nivolumab, compared with 30 minutes for IV administration.

The possibility of faster administration times—without the need for an infusion center—could make the PD-1 inhibitor available to patients for whom access is difficult, including those in rural areas, an expert told the National Cancer Institute (NCI) earlier this year.³

“Subcutaneous immunotherapy is exciting on many fronts,” Mark Ball, MD, a kidney cancer expert in NCI’s Center for Cancer Research said in March. “We don't know if this is going to end up being a game changer or not, but it definitely has potential.”

References

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News Release. Bristol Myers Squibb. May 8, 2024. Accessed May 6, 2024. https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx
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. 2024;42(suppl 4). doi:0.1200/JCO.2024.42.4_suppl.LBA360
3. Jaber N. Nivolumab injections could make treatment easier for more people with cancer. National Cancer Institute. March 13, 2024. Accessed May 9, 2024. https://www.cancer.gov/news-events/cancer-currents-blog/2024/kidney-cancer-subcutaneous-nivolumab