Subcutaneous Nivolumab Maintains Comparable Efficacy, Safety to IV in ccRCC

Subcutaneous nivolumab was previously approved for use in solid tumors.

Nivolumab with hyaluronidase-nvhy (Opdivo Qvantig; subcutaneous nivolumab) displayed comparable efficacy, safety, and tolerably compared with intravenous (IV) nivolumab (Opdivo) in previously treated, advanced or metastatic clear cell renall cell carcinoma (ccRCC), per updated results from the phase 2 CheckMate-67T trial (NCT04810078), which were presented at the 50th Annual Oncology Nursing Congress.¹

Results showed that at a minimum follow-up of 15 months, the overall response rate (ORR) was 27% for subcutaneous nivolumab (n = 248) vs 21% for IV nivolumab (n = 247). ORR was a key secondary end point powered for noninferiority. Notably, the study previously met its co-primary end points of time-averaged serum concentration over the first 28 days and minimum serum concentration at steady state during the primary analysis.^1,2

Additional data from the updated analysis showed that the median progression-free survival (PFS) was 6.3 months with subcutaneous nivolumab vs 5.7 months with the IV formulation. The median time to response was 3.7 months in both arms. Six- and 12-month overall survival (OS) rates were 84% and 72%, respectively, for subcutaneous nivolumab, compared with 86% and 73%, respectively, for IV nivolumab.

"CheckMate-67T met its co-primary end points and key powered secondary end point at the primary analysis, demonstrating pharmacokinetic and efficacy noninferiority of subcutaneous nivolumab to IV nivolumab, " lead study author Daniel Adamczyk, PharmD, RPh, of Bristol Myers Squibb, and colleagues wrote in a poster presentation of the data. "These data further support the use of subcutaneous nivolumab as a new option with reduced administration time to improve patient treatment experience and health care efficiency."

In December 2024, the FDA approved subcutaneous nivolumab for use across approved adult solid tumor IV nivolumab indications as monotherapy; as monotherapy maintenance following completion of nivolumab plus ipilimumab (Yervoy) combination therapy; or in combination with chemotherapy or cabozantinib (Cabometyx).³ This regulatory decision was based on previously reported data from CheckMate-67T.

CheckMate-67T Design

CheckMate-67T evaluated the safety and efficacy of subcutaneous nivolumab compared with the standard IV formulation in patients with previously treated advanced or metastatic ccRCC. Eligible patients had experienced disease progression during or after at least 1 prior systemic regimen and had not previously received immuno-oncology therapy. Additional eligibility criteria included a Karnofsky performance status of at least 70.

Enrolled patients were randomly assigned in a 1:1 ratio to receive either subcutaneous nivolumab at 1200 mg co-formulated with recombinant human hyaluronidase PH20 at 20,000 units every 4 weeks; or IV nivolumab at 3 mg/kg every 2 weeks. Patients continued treatment until disease progression, unacceptable toxicity, withdrawal of consent, completion of 2 years of treatment, or death.

Beyond the co-primary pharmacokinetic end points and the key secondary end point of ORR, DOR, disease control rate, PFS, and OS were other secondary end points assessed by blinded independent central review. Safety assessments included the incidence of adverse effects (AEs), treatment-related AEs (TRAEs), injection-site reactions, and treatment discontinuations due to AEs or TRAEs.

The study enrolled patients across 75 sites in 17 countries. Baseline characteristics and efficacy outcomes were evaluated in all randomized patients, while safety analyses included all patients who received at least one dose of nivolumab. Baseline patient demographics and disease characteristics were similar between the 2 arms.

Safety Analysis

Among patients treated with subcutaneous nivolumab (n = 247), any-grade AEs occurred in 93.1% of patients (grade 3/4, 40.1%) compared with 94.3% (grade 3/4, 46.5%) for those given the IV formulation (n = 245). TRAEs of any grade were reported in 61.5% of patients in the subcutaneous arm, including 11.7% who experienced grade 3/4 TRAEs. Any-grade TRAEs occurred in 65.7% of patients in the IV arm, including 17.1% who had grade 3/4 TRAEs.

Discontinuation due to any AE occurred in 12.6% of patients in the subcutaneous arm, including 4.5% who discontinued treatment due to TRAEs. These respective rates were 13.9% and 5.3% in the IV arm.

Immune-modulating medication was administered to 71.9% of patients who experienced an immune-mediated AE in the IV arm (n = 64), and 32.8% of these patients received corticosteroids equivalent to at least 40 mg prednisone. These rates were 70.8% and 49.2%, respectively in the IV arm (n = 65).

Select any-grade TRAEs in the subcutaneous nivolumab group included endocrine-related AEs at 12.6% (grade 3/4, 0.8%), gastrointestinal AEs at 6.1% (1.2%), hepatic events at 9.3% (1.2%), pulmonary events at 4.9% (1.6%), renal events at 1.2% (0.4%), skin-related events at 24.3% (1.2%), and hypersensitivity or infusion reactions at 2.4% (0.4%).

In the IV group, any-grade TRAEs included endocrine-related AEs at 18.0% (grade 3/4, 1.2%), gastrointestinal effects in 6.9% (0.4%), hepatic effects in 12.7% (1.2%), pulmonary effects in 3.3% (0.8%), renal effects in 2.4% (0.4%), skin-related effects in 27.3% (1.2%), and hypersensitivity or infusion reactions in 2.7% (0.4%).

Notably, treatment-related local injection site reactions (LISRs) were reported in 5% of patients in the subcutaneous arm vs 2% of patients in the IV arm. Five patients in the subcutaneous group needed intervention for LISRs, including 4 who received topical corticosteroids. All LISRs reported in the subcutaneous arm were grade 1, except for a single grade 2 occurrence.

References

1. Adamczyk D, Bourlon MT, Albiges L, Yu Z, George S. Updated efficacy and safety results from CheckMate 67T: nivolumab subcutaneous vs intravenous in patients with previously treated advanced or metastatic clear cell renal cell carcinoma. Presented at: 50th Annual Oncology Nursing Society Congress; April 9-13, 2025; Denver, CO. Abstract 16944.
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):LBA360. doi:10.1200/JCO.2024.42.4_suppl.LBA360
3. FDA approves nivolumab and hyaluronidase-nvhy for subcutaneous injection. FDA. December 27, 2024. Accessed April 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-and-hyaluronidase-nvhy-subcutaneous-injection