Subcutaneous nivolumab approved in EU, Canada for solid tumors

The European Commission (EC) and Health Canada have approved the subcutaneous (SC) formulation of nivolumab (Opdivo), co-formulated with recombinant human hyaluronidase (rHuPH20; Enhanze), across several previously approved solid tumor indications.^1,2,3

Subcutaneous nivolumab was approved by the FDA in December 2024.

This includes nivolumab as a monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab (Yervoy) combination therapy, or in combination with chemotherapy or cabozantinib (Cabometyx). Nivolumab is currently approved across several indications in renal cell carcinoma (RCC) and urothelial carcinoma.

Nivolumab SC should not be offered concurrently with ipilimumab.

“The EC’s decision to approve Opdivo SC ushers in a new era of cancer care in which we are able to deliver a 3- to 5-minute injection of a treatment that has shown consistent efficacy and comparable safety to intravenous Opdivo, which changed the cancer treatment landscape over a decade ago,” said Dana Walker, MD, MSCE, Opdivo global program lead at Bristol Myers Squibb (BMS), in a news release on the EC approval.¹ “BMS is committed to advancing medicines that help improve the patient experience, and with the approval of Opdivo SC in the European Union, we are delivering on this goal.”

The EC approval is valid across all 27 of the European Union member states as well as in Iceland, Liechtenstein, and Norway.

On the approval in Canada, Hamilton-based medical oncologist Sebastien Hotte, MD, MSc (HRM), FRCPC, said, "This approval represents a meaningful advancement for patients with solid tumors and the teams that care for them. Subcutaneous delivery of nivolumab has the potential to help reduce pressure on clinic resources and streamline workflows, offer added convenience to patients, and facilitate administration of immunotherapy especially in the maintenance phase of treatment plans."³

Subcutaneous nivolumab, co-formulated with rHuPH20, (marketed as Qvantiq) was approved by the FDA in December 2024.

Data on Subcutaneous Nivolumab

The approvals are supported by findings from the phase 3 CheckMate-67T trial (NCT04810078), in which subcutaneous nivolumab with rHuPH20 met the study’s coprimary end points by demonstrating noninferiority to intravenous (IV) nivolumab regarding time-averaged nivolumab serum concentration over 28 days (Cavgd28; geometric mean ratio [GMR], 2.10; 90% CI, 2.00 to 2.20) and minimum serum concentration at a steady state (Cminss; GMR, 1.77; 90% CI, 1.63 to 1.93) in patients with advanced or metastatic clear cell RCC (ccRCC).⁴

Data from the study also showed that subcutaneous nivolumab demonstrated noninferiority to IV nivolumab in the key powered secondary end point of objective response rate (ORR). Specifically, patients in the subcutaneous arm demonstrated an ORR of 24.2% (95% CI, 19.0 to 30.0) per blinded independent central review (BICR), compared with 18.2% (95% CI, 13.6 to 23.6) among patients in the IV arm.

Additionally, the median progression-free survival per BICR was 7.23 months (95% CI, 5.13 to 7.49) in the subcutaneous arm vs 5.65 months (95% CI, 5.29 to 7.39) in the IV arm.

The safety profile for subcutaneous nivolumab was consistent with that of the IV formulation. Serious adverse events (AEs) were reported in 28% of patients in the subcutaneous arm, which included pleural effusion (1.6%), pneumonitis (1.6%), hyperglycemia (1.2%), hyperkalemia (1.2%), hemorrhage (1.2%) and diarrhea (1.2%).

Among patients who received the subcutaneous formulation, 8.1% experienced injection-site reactions, with all being low-grade and transient. AEs led to treatment discontinuation in 10% of patients.

Deaths due to study drug toxicity occurred in 3 patients in the subcutaneous arm and 1 patient in the IV arm. Most deaths that occurred during the study were due to disease progression.

In total, the phase 3, open-label CheckMate-67T trial enrolled 495 patients with advanced or metastatic ccRCC who had received prior systemic therapy. Patients were randomly assigned 1:1 to receive 1200 mg subcutaneous nivolumab plus hyaluronidase-nvhy every 4 weeks (n = 248) or to 3 mg/kg IV nivolumab every 2 weeks (n = 247) for up to 2 years of treatment or until disease progression, unacceptable toxicity, withdrawal, completion of 2 years of treatment, or death.

The coprimary pharmacokinetic end points for noninferiority testing were Cavgd28 and Cminss of subcutaneous nivolumab vs IV nivolumab. The key secondary end point was ORR per BICR.

REFERENCES

1. Bristol Myers Squibb receives European Commission approval for the subcutaneous formulation of Opdivo (nivolumab) across multiple solid tumor indications. News release. Bristol Myers Squibb. May 28, 2025. Accessed May 28, 2025. https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Receives-European-Commission-Approval-for-the-Subcutaneous-Formulation-of-Opdivo-nivolumab-Across-Multiple-Solid-Tumor-Indications/default.aspx

2. Halozyme announces Bristol Myers Squibb received European Commission approval for subcutaneous Opdivo (nivolumab) co-formulated with Enhanze across multiple solid tumor indications. News release. Halozyme Therapeutics Inc. May 28, 2025. Accessed May 28, 2025. https://www.prnewswire.com/news-releases/halozyme-announces-bristol-myers-squibb-received-european-commission-approval-for-subcutaneous-opdivo-nivolumab-co-formulated-with-enhanze-across-multiple-solid-tumor-indications-302466295.html

3. New subcutaneous formulation of Opdivo approved in Canada for use across all authorized solid tumour indications. News release. Bristol Myers Squibb Canada. May 27, 2025. Accessed May 28, 2025. https://www.biospace.com/press-releases/new-subcutaneous-formulation-of-opdivo-approved-in-canada-for-use-across-all-authorized-solid-tumour-indications

4. 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):LBA360. doi:10.1200/JCO.2024.42.4_suppl.LBA360