FDA Approval of Subcutaneous Nivolumab Represents Paradigm Shift in Solid Tumor Management

Roxana S. Dronca, MD

The FDA approval of nivolumab and hyaluronidase-nvhy (Opdivo Qvantig; subcutaneous nivolumab) marks a paradigm shift toward a focus on improving the treatment experience for patients with solid tumors without compromising the efficacy of therapy, according to Roxana S. Dronca, MD.

On December 27, 2024, the regulatory agency approved subcutaneous nivolumab across approved adult solid tumor indications as monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab (Yervoy) combination therapy, or in combination with chemotherapy or cabozantinib (Cabometyx).¹

The approval includes indications for renal cell carcinoma (RCC), melanoma, non–small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma, esophageal carcinoma, gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

The regulatory decision was supported by data from the phase 3 CheckMate-67T trial (NCT04810078), which showed that the lower boundary of the 90% confidence interval of geometric mean ratios (GMRs) was not less than 0.8 for both serum nivolumab C_avg over 28 days (GMR, 2.098; 90% CI, 2.001-2.200) and C_min at steady state (GMR, 1.774; 90% CI, 1.633-1.927) for the subcutaneous formulation (n = 242) vs the IV formulation (n = 245) in patients with pretreated advanced RCC.^1,2

Additionally, patients treated with subcutaneous nivolumab experienced an overall response rate (ORR) of 24% (95% CI, 19%-30%) vs 18% (95% CI, 14%-24%) for those treated with IV nivolumab (Opdivo).¹

“Developing patient-friendly methods of administering cancer therapies, which allow for delivery closer to patients' communities or [potentially] in their homes, represents a significant paradigm shift in oncology,” Dronca explained. She is a hematologist/oncologist and chair of the Department of Hematology/Oncology at the Mayo Clinic Comprehensive Cancer Center in Jacksonville, Florida.

In an interview with OncLive^®, Dronca discussed how the approval of subcutaneous nivolumab represents a significant shift in cancer management; detailed the findings derived from CheckMate-67T; and explained how the continued development of subcutaneous therapies could affect patient care.

OncLive: What is the significance of the approval of subcutaneous nivolumab across solid tumor indications?

Dronca: The approval of subcutaneous nivolumab represents a shift in how cancer treatments are delivered and conceptualized. [The approval] sets the stage for a broader acceptance of subcutaneous therapies in solid tumors, as [subcutaneous administrations] are already happening more in hematological malignancies. [Subcutaneous agents] are transforming our treatment landscape to prioritize clinical outcomes and patient convenience, quality of life, experience with care, and accessibility, which is very important.

How does the delivery of subcutaneous nivolumab differ from the IV formulation?

Traditional IV administration of nivolumab or other treatments requires our patients to spend prolonged time in infusion chairs and a long time in the clinic. Some patients need a port-a-cath, which places a lot of strain on our patients, both physically and emotionally, especially for people who receive treatment every few weeks for a number of years. This cumulative burden [with IV administration] is impactful and significant for our patients.

Transitioning to a simplified subcutaneous formulation of nivolumab will allow our patients to have a much shorter injection time and, ultimately, a shorter time in the clinic, [and this could] potentially offer options for delivering treatment outside of infusion units. Maybe these injections can be administered directly in the clinic where the patient is seen, [allowing them to] skip the additional step of checking into the chemotherapy unit and having the treatment administered there. Potentially, we can envision a future where these treatments will be given in alternative health care settings, [such as] settings closer to where the patient lives, [either] in primary care offices or at home.

This [approval] has broad implications for access to care, especially in reducing health care disparities for patients who live far from treatment centers and for [those] juggling other work and family [responsibilities]. [Helping them save] the time [it takes to] travel to and from facilities, or the time they spend in the clinic, is meaningful.

What patient population was enrolled in the CheckMate-67T trial, and what were the key findings?

CheckMate-67T was a multicenter, open-label, randomized trial that assessed the noninferiority of subcutaneous nivolumab compared with IV nivolumab. It enrolled 495 patients with metastatic or advanced RCC that progressed after 1 or 2 lines of systemic therapy; [prior treatment] with immunotherapy [was not allowed]. Patients also had a Karnofsky performance status of 70 or higher.

Patients were randomly assigned 1:1 to receive either subcutaneous nivolumab—1200 mg of subcutaneous nivolumab formulated with recombinant human hyaluronidase at 20,000 units—every 4 weeks; or IV nivolumab at 3 mg/kg every 2 weeks. [Treatment continued] until progression, unacceptable toxicity, consent withdrawal, or completion of 2 years of therapy, which is standard for clinical trials in immuno-oncology.

The primary [objective] was the noninferiority in terms of exposure to subcutaneous nivolumab compared with IV nivolumab. There were two coprimary pharmacokinetic end points for noninferiority, which were C_avg over 28 days and C_min at steady state. There was also a powered secondary end point, which was ORR compared between subcutaneous and IV nivolumab.

The trial met both coprimary endpoints, and it also met the secondary end point of ORR, which was 24% for subcutaneous nivolumab and 18% for IV nivolumab [as] evaluated by blinded independent central review.

Are there any differences in safety profiles between IV and subcutaneous nivolumab?

We [currently] have a clinical trial [using] subcutaneous nivolumab open at [Mayo Clinic], and I get this question [about safety] from our patients all the time. [CheckMate-67T] showed that the safety profiles of subcutaneous and IV nivolumab are very comparable. There were no new safety signals [with the subcutaneous formulation].

The most common [adverse] effects [AEs] on both arms were fatigue, musculoskeletal pain, rash, and cough; [these are AEs] we would expect with IV nivolumab. They did see an 8% rate of [any-grade] local injection site reactions with subcutaneous nivolumab, which were all very mild, low grade, and transient. Again, [the safety profile of subcutaneous nivolumab] is very comparable with our experience [with the IV formulation] in the clinic.

How does this approval potentially open doors for other therapies to be delivered subcutaneously?

This approval of subcutaneous nivolumab sets a precedence for the development and adoption of more subcutaneous cancer-directed therapies, especially for solid tumors. [Data from CheckMate-67T] show the feasibility of formulating highly effective IV therapies into much more patient-friendly, simple, and convenient administrations without compromising efficacy or safety.

[This approval] will open the door for more drugs to be formulated and delivered in much more patient-friendly ways, [allowing us] to prioritize patient convenience, time, and quality of life with clinical outcomes. From a health system perspective, [this approval] highlights the need for the development of drugs to allow us to be more efficient in delivering care, as the number of patients with cancer is increasing.

It's estimated that by 2040, for example, there will be 50% more new cancer diagnoses. Patients also live a lot longer because of developments in diagnostics and treatments, and they receive subsequent lines of treatment. We are [currently] outpaced in our ability to deliver treatment to patients, and we have to find therapies that allow us to be much more efficient. If we remove a lot of the resources that we use today for IV administration of many drugs and save those resources by treating more patients and allowing our nurses to focus more on patients, health care systems become stronger.

[Subcutaneous nivolumab provides] a perfect balance between addressing a need in quality of life with convenience and access, and it also addresses a health care need in being able to provide therapies to more patients.

References

1. FDA approves nivolumab and hyaluronidase-nvhy for subcutaneous injection. FDA. December 27, 2024. Accessed January 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-and-hyaluronidase-nvhy-subcutaneous-injection
2. Albiges L, Bourlon MT, Chacón M, et al. Subcutaneous versus intravenous nivolumab for renal cell carcinoma. Ann Oncol. Published online September 15, 2024. doi:10.1016/j.annonc.2024.09.002