FDA Approves Subcutaneous Nivolumab in Advanced or Metastatic Solid Tumors

FDA

The FDA has approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig; subcutaneous nivolumab) for subcutaneous injection across approved adult, solid tumor nivolumab (Opdivo) 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. Opdivo Qvantig is not indicated in combination with intravenous ipilimumab.

The regulatory decision was supported by data from the phase 3 CHECKMATE-67T trial (NCT04810078), which showed that the lower boundary of 90% confidence interval of geometric mean ratios was not less than 0.8 for both serum nivolumab C_avg over 28 days and C_min at steady state. In the subcutaneous nivolumab arm (n = 242), the geometric mean of Cavg over 28 days was 77.373 μg/ml (90% CI, 74.555-80.297) vs 36.875 μg/ml (90% CI, 35.565-38.235) in the intravenous (IV) nivolumab arm (n = 245; GMR, 2.098; 90% CI, 2.001-2.200).2 The geometric mean of C_min at steady state was 122.227 μg/ml (90% CI, 114.552-130.416) in the subcutaneous arm vs 68.901 μg/ml (90% CI, 64.676-73.402) in the IV arm (GMR, 1.774; 90% CI, 1.633-1.927).

Patients with advanced or metastatic clear cell RCC treated with subcutaneous nivolumab experienced an overall response rate (ORR) of 24% (95% CI, 19%-30%) compared with 18% (95% CI, 14%-24%) for those treated with intravenous nivolumab.¹

The open-label, multicenter, randomized, noninferiority CheckMate 67T trial enrolled patients at least 18 years of age with histologically confirmed advanced or metastatic clear cell RCC with or without sarcomatoid features who experienced intolerance or progression on or after the prior treatment regimen and within 6 months of randomization.² Patients needed to be naive to checkpoint inhibitors, and up to 2 prior lines of therapy were allowed. A Karnofsky performance status of at least 70 was necessary.

Patients were randomly assigned to receive subcutaneous nivolumab consisting of nivolumab at a flat dose of 1200 mg coformulated with hyaluronidase at 20,000 units every 4 weeks; or IV nivolumab at 3 mg/kg every 2 weeks per dosing guidelines at the time of study initiation. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, 2 years of treatment, or death.

Noninferiority of C_avg over 28 days and C_min at steady state served as the trial's primary end points. Secondary end points included ORR, disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety.

DCR, TTR, PFS, and OS data were numerically similar between the 2 arms.

The safety profiles were similar for subcutaneous and intravenous nivolumab.¹ In the subcutaneous arm, the most common adverse effects reported in at least 10% of patients included fatigue, musculoskeletal pain, pruritus, rash, and cough.

The recommended dose for subcutaneous nivolumab is indication-specific: 600 mg of nivolumab and 10,000 units of hyaluronidase once every 2 weeks; 900 mg of nivolumab and 15,000 units of hyaluronidase once every 3 weeks; or 1200 mg of nivolumab and 20,000 units of hyaluronidase once every 4 weeks until disease progression, unacceptable toxicity, or as indicated in the prescribing information.

References

1. FDA approves nivolumab and hyaluronidase-nvhy for subcutaneous injection. FDA. December 27, 2024. Accessed December 27, 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