FDA approves subcutaneous nivolumab for solid tumors, including RCC

The FDA has approved nivolumab (Opdivo) plus hyaluronidase-nvhy (Qvantig) for subcutaneous injection across previously approved solid tumor indications for nivolumab as a monotherapy, monotherapy maintenance following completion of combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).¹

Nivolumab was previously approved under several indications in RCC.

Nivolumab was previously approved under several indications in renal cell carcinoma (RCC) and urothelial carcinoma.

The approval is supported by findings from the phase 3 CheckMate-67T trial (NCT04810078), in which subcutaneous nivolumab plus hyaluronidase-nvhy met the study’s co-primary end points by demonstrating noninferiority to IV nivolumab regarding time average nivolumab serum concentration over 28 days (C_avgd28; geometric mean ratio [GMR}, 2.098; 90% CI, 2.001-2.200) and minimum serum concentration at a steady state (C_minss; GMR, 1.774; 90% CI, 1.633-1.927).² For both pharmacokinetic end points, the predefined acceptance margin was met, with the lower boundary of the 90% confidence interval of geometric mean ratios not reaching less than 0.8.

Data from the study, which were presented earlier this year at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California,² 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, 19.0-30.0) per blinded independent central review (BICR), compared with 18.2% (95% CI, 13.6-23.6) among patients in the IV arm.

The safety profile for subcutaneous nivolumab was consistent with that of the IV formulation. Among patients who received the subcutaneous formulation, 8.1% experienced injection-site reactions, with all being low-grade and transient. 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, or death.

The co-primary pharmacokinetic end points for noninferiority testing were C_avgd28 and C_minss of subcutaneous nivolumab vs IV nivolumab. The key secondary end point was ORR per BICR.

The CheckMate-67T remains ongoing, with final completion expected in January 2026.³

Indications

Subcutaneous nivolumab plus hyaluronidase-nvhy are approved across most previously approved adult solid tumor indications for nivolumab, including several in RCC and urothelial carcinoma.

In RCC, subcutaneous nivolumab is approved for the first-line treatment of patients with intermediate- or poor-risk advanced RCC following treatment with intravenous (IV) nivolumab and ipilimumab combination therapy, in combination with cabozantinib for the first-line treatment of patients with advanced RCC, and in the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy. Subcutaenous nivolumab is not approved in combination with ipilimumab for the treatment of patients with RCC.

In urothelial carcinoma, the subcutaneous nivolumab formulation is indicated for the treatment of patients with urothelial carcinoma who are at high risk of recurrence following radical tumor resection, in locally advanced or metastatic urothelial carcinoma in patients that have progressed during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, and in combination with cisplatin and gemcitabine for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma.⁴

References

1. FDA approves nivolumab and hyaluronidase-nvhy for subcutaneous injection. News release. Published online and accessed December 27, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-and-hyaluronidase-nvhy-subcutaneous-injection

2. George S, Bourlon TB, 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. doi:10.1200/JCO.2024.42.4_suppl.LBA360

3. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Last updated March 1, 2024. Accessed December 27, 2024. https://clinicaltrials.gov/study/NCT04810078

4. U.S. Food and Drug Administration approves Opdivo Qvantig (nivolumab and hyaluronidase-nvhy) injection, for subcutaneous use in most previously approved adult, solid tumor Opdivo (nivolumab) indications. News release. Bristol Myers Squibb. Published online and accessed December 27, 2024. https://www.businesswire.com/news/home/20241218841283/en/U.S.-Food-and-Drug-Administration-Approves-Opdivo-Qvantig%E2%84%A2-nivolumab-and-hyaluronidase-nvhy-Injection-for-Subcutaneous-Use-in-Most-Previously-Approved-Adult-Solid-Tumor-Opdivo%C2%AE-nivolumab-Indications12