Reading time: 6 minutes

Brittane L. Strahan MSN, RN, CCRP

The treatment of solid tumors is evolving constantly and rapidly in the vast oncology clinical research landscape. Though huge strides have been made in the treatment of even difficult tumor types (such as small cell lung cancer), there is still much work left to do. In the last decade, cancer treatments have become more precise and  patient outcomes have continued to improve. Now, a key question is– how can we make cancer treatments even simpler, more cost-effective, and more patient-friendly?¹ 

In this short post, we will look at the first, and only, approved immune-targeting drug that can be given under the skin to treat a solid tumor. We will review the basics of using cancer treatments that target the immune system before diving into the newly approved medication, how it is given, the data that supported its approval, and lastly– why it all matters.

Immunotherapy as a cancer treatment

In 2018, two individuals were awarded the Nobel Prize in Physiology or Medicine for their discovery of the function and benefits of checkpoint inhibition for cancer treatments. Checkpoint inhibitors are immunotherapy drugs that work by blocking checkpoint proteins on cancer cells. What does this mean and why does it matter? Checkpoint proteins can dampen the immune response to cancer cells and allow for tumor growth. Normally, our immune systems recognize foreign cells such as bacteria, virus, fungi, or an abnormal body cell. However, in the case of some cancers, cellular changes, including those related to cellular proteins, can cause the immune system to bypass cancerous cells.⁶ 

This can happen in two ways. The first occurs when the checkpoint proteins cause T cells (part of the immune system) to become overly active. In this case, T cells may start to destroy healthy body tissues. Second, sometimes cancer cells can signal for the T cells to become inactive. This hinders the T cells from recognizing and destroying the cancer cells. Checkpoint inhibitors are designed to regulate the protein amounts and activity, thus preserving the normal response of the T cells. This ability to harness the immune system’s power to recognize and destroy cancer cells has been a boon to cancer therapeutics.^5,6

Nivolumab and hyaluronidase-nvhy

Of the 50 new drugs approved by the FDA last year, 14 were approved for hematology and oncology.² One of the  most recently approved of 2024 was a combination of nivolumab and hyaluronidase-nvhy. These medications (one a potent antibody blocker (PD-1) on the market for 25 different indications and one an enzyme used to break down body tissues including connective tissues, skin, and fluids) work in tandem to deliver a highly effective chemotherapeutic in a non-intravenous (IV) form. While nivolumab activates the immune system, the hyaluronidase-nvhy facilitates a better distribution of nivolumab into the subcutaneous tissue.⁷

Administration

This combination therapy is given subcutaneously (under the skin) and does not require a long treatment time or an IV catheter. Compared to the 30 minute treatment required for an IV dose of nivolumab, it only takes between three and five minutes to give this new combination.³ This shorter administration makes receiving treatment more convenient for the patient and frees up resources for the oncology clinic. Even better, this combination drug is approved for any solid tumor in which nivolumab can be given. It can be given alone, as maintenance therapy following IV nivolumab and ipilimumab (another drug which interacts with the immune system), or in combination with chemotherapy or cabozantinib (a medication which blocks cancer cell replication).⁴ This is the first, and currently only, approved subcutaneous PD-1 inhibitor.³

In addition, by eliminating the need for  IV access or a mediport, there is less risk for infection and vein irritation.⁷

Support for approval

This FDA approval was stimulated by data from the Phase 3 CheckMate-67T trial (NCT04810078) which evaluated the use of IV nivolumab versus the subcutaneous combination.⁸ Although this trial is still actively recruiting, a blinded independent interim data analysis showed that 24% of patients receiving the subcutaneous combination had a positive response in their tumor (decreasing size) compared to 18% receiving IV nivolumab. The safety profile was comparable between the two medications. Complications of the combined therapy included fatigue, muscle and joint pain, itching, rash, and cough which are all known side effects of nivolumab.⁴ 

Findings reported at the 2022 American Society of Clinical Oncology (ASCO) meeting and those found in an updated 2024 report from the European Society of Medical Oncology (ESMO) also support these clinical results .^7,9 

Why does it matter?

There are many checkpoint inhibitor medications on the market, so why does the combination therapy of nivolumab and hyaluronidase-nvhy matter? 

Firstly, as illustrated above, the time for administration is much shorter (5 versus 30 minutes). This is more convenient for the patient and does not require them to be in the treatment room (and utilizing resources) for long periods of time. Oncology clinics see many patients a day, so freeing up a nurse and room for another patient is a good use of resources. This alone benefits both the patient and the system (staff and infrastructure). Perhaps, like some other subcutaneous medications, it may one day even be available for self-administration.¹ Secondly, the response rate was slightly better in the group receiving the subcutaneous form of the medication versus the IV form. Finally, this medication has a similar safety profile to IV nivolumab, making it a reasonable choice for treating all cancers for which nivolumab is approved. Each of these reasons make this an appealing treatment option and a great addition to the immunotherapy toolbox.

Wrapping it up

Nivolumab and hyaluronidase-nvhy is one of the most recently approved drugs in cancer therapeutics. Able to be given for any approved indication for IV nivolumab, this new therapy can reduce strain on the patient (treatment burden) and the health care system (resource utilization). With comparable safety profiles and slightly higher response rates in the clinical trials interim analysis, this medication looks like a great alternative to the older standby immunotherapy nivolumab.

Header Image Source: retrieved from Unsplash.com

Edited by Melanie Padalino

References

1. Bittner B, Richter W, Schmidt J. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities. BioDrugs. 2018;32(5):425-440. doi:10.1007/s40259-018-0295-0 
2. Research C for DE and. Novel drug approvals for 2024. FDA. Published online January 8, 2025. Accessed January 10, 2025. https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024 
3. Halozyme Therapeutics Inc. Halozyme announces fda approval of bristol myers squibb’s opdivo qvantig^TM with enhanze® for subcutaneous use in most previously approved adult solid tumor opdivo® (Nivolumab) indications. Accessed January 10, 2025.  https://www.prnewswire.com/news-releases/halozyme-announces-fda-approval-of-bristol-myers-squibbs-opdivo-qvantig-with-enhanze-for-subcutaneous-use-in-most-previously-approved-adult-solid-tumor-opdivo-nivolumab-indications-302339837.html 
4. Research C for DE and. FDA approves nivolumab and hyaluronidase-nvhy for subcutaneous injection. FDA. Published online December 27, 2024. Accessed January 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-and-hyaluronidase-nvhy-subcutaneous-injection 
5. Musetti S, Das M. Cancer immunotherapy wins the 2018 nobel prize. OncoBites. October 2, 2018. Accessed January 10, 2025. https://oncobites.blog/2018/10/02/cancer-immunotherapy-wins-the-2018-nobel-prize/ 
6. Cancer Research UK. Checkpoint inhibitors. Accessed January 10, 2025. https://www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/types/checkpoint-inhibitors 
7. Chacon MR, Cutuli HJ, Bracarda S, et al. Subcutaneous nivolumab versus intravenous nivolumab in patients with previously treated, advanced, or metastatic clear cell renal cell carcinoma. JCO. 2022;40(16_suppl):TPS4621-TPS4621. doi:10.1200/JCO.2022.40.16_suppl.TPS4621 
8. Bristol Myers Squibb. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread | bms study connect. Accessed January 10, 2025. https://www.bmsstudyconnect.com/it/en/clinical-trials/NCT04810078.html 
9. Albiges L, Bourlon de los Rios MT, Chacon M, et al. 1691P Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients (pts) with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Updated efficacy and safety results from CheckMate 67T. Annals of Oncology. 2024;35(2):S1013-S1014. https://www.annalsofoncology.org/article/S0923-7534(24)03303-9/fulltext