FDA Accepts Biologics License Application for Subcutaneous Formulation of Nivolumab


The new administration method, which is co-formulated with rHuPH20, is usable in previous approved nivolumab indications for solid tumors in adult patients.

The FDA has accepted a biologics license application (BLA) for a subcutaneous formulation of nivolumab (Opdivo; Bristol Myers Squibb) co-formulated with a proprietary recombinant human hyaluronidase (rHuPH20; Halozyme) across all previously approved nivolumab indications for solid tumors in adults. This includes monotherapy, maintenance monotherapy following treatment with the combination of nivolumab plus ipilimumab (Yervoy; Bristol Myers Squibb), and combination therapy with chemotherapy or cabozantinib. Additionally, the FDA assigned a prescription drug user fee act for the subcutaneous formulation of nivolumab with a goal date of December 29, 2024.1

Health care professional preparing injection -- Image credit: REDPIXEL | stock.adobe.com

Image credit: REDPIXEL | stock.adobe.com

Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to use the body’s own immune system to help restore anti-tumor immune response. It has previously been approved in a variety of tumors—either on its own or combined with other therapies—including unresectable or metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, and metastatic or locally advanced urothelial carcinoma, among other indications.1

“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,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in a press release. “[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

About the Trial

Trial Name: A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advanced or Has Spread (CheckMate-67T)

ClinicalTrials.gov ID: NCT04810078

Sponsor: Bristol-Myers Squibb

Completion Date (Estimated): January 29, 2026

The acceptance was based on the open-label, randomized phase 3 CheckMate-67T (NCT04810078) trial that evaluated the subcutaneous formulation of nivolumab co-formulated with rHuPH20 and compared it with intravenous (IV) nivolumab in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior systemic therapy. The trial examined 495 patients who were randomly assigned to receive either subcutaneous nivolumab co-formulated with rHuPH20 or intravenous nivolumab. The trial’s co-primary end points are time-averaged serum concentration over 28 days (Cavgd28) and trough serum concentration at steady-state (Cminss) of subcutaneous nivolumab over IV nivolumab. The trial’s secondary end point is objective response rate (ORR).1-3

The trial, according to investigators, met both its co-primary and secondary end points, with subcutaneous nivolumab demonstrating noninferiority of Cavgd28 and Cminss, as well as ORR. CheckMate-67T’s safety, efficacy, and pharmacokinetic results were presented at the American Society of Clinical Oncology 2024 Genitourinary Cancers Symposium.1,2

“IV [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. We are delighted that the results of CheckMate-67T demonstrate that subcutaneous nivolumab delivers noninferior pharmacokinetics, in addition to objective response rate and safety data consistent with IV [nivolumab],” said Fusaro in another press release.3

Adverse events (AEs) reported by patients who were treated with nivolumab include immune-mediated pneumonitis, endocrinopathies (eg, thyroid disorders, hypophysis, diabetes, adrenal insufficiency), colitis, dermatologic complications, nephritis with renal dysfunction, as well as infusion-related AEs. Serious AEs such as abdominal pain, hyponatremia, pneumonia, diarrhea, musculoskeletal pain, and acute kidney injury were reported by patients enrolled in clinical trials; however, the most common AEs reported among participants were rash, constipation, vomiting, nausea, headache, and upper respiratory tract infection.1,3

“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 to 5 minutes rather than a 30- to 60-minute infusion,” said Fusaro in the press release.1

In addition to ccRCC, nivolumab has shown effectiveness in a variety of tumor types. For instance, data have found found that nivolumab plus chemotherapy before surgery is effective in delaying the progression or return of the cancer. In the CheckMate 816 trial, participants with early-stage NSCLC who received neoadjuvant nivolumab and chemotherapy lived longer without experiencing serious adverse events, including the return of their cancer. These findings led to the March 2022 FDA approval of nivolumab as a neoadjuvant treatment in combination with chemotherapy for individuals with early-stage NSCLC.4


1. Bristol Myers Squibb. U.S. Food and Drug Administration Accepts Bristol Myers Squibb’s Application for Subcutaneous Nivolumab (nivolumab and hyaluronidase). News release. May 6, 2024. Accessed May 6, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx
2. A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advanced or Has Spread (CheckMate-67T). ClinicalTrials.gov identifier: NCT04810078. Updated March 1, 2024. Accessed May 6, 2024. https://clinicaltrials.gov/study/NCT04810078
3. McGovern, G. Phase 3 Trial Results Support Subcutaneous Nivolumab Treatment for Patients With Metastatic ccRCC. Pharmacy Times. October 20, 2023. Accessed May 6, 2024. https://www.pharmacytimes.com/view/phase-3-trial-results-support-subcutaneous-nivolumab-treatment-for-patients-with-metastatic-ccrcc
4. For Early-Stage Lung Cancer, Nivolumab and Chemo before Surgery Proves Effective. National Cancer Institute. May 20, 2022. Accessed May 6, 2024. https://www.cancer.gov/news-events/cancer-currents-blog/2022/nivolumab-chemotherapy-neoadjuvant-lung-cancer
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