CHMP Recommends Approval of Subcutaneous Nivolumab in Multiple Solid Tumors

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The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a recommendation of approval for the subcutaneous formulation of nivolumab (Opdivo) co-formulated with recombinant human hyaluronidase (rHuPH20).1 The indication would cover the use of subcutaneous nivolumab in adult patients with solid tumors as monotherapy; monotherapy maintenance following completion of nivolumab plus ipilimumab (Yervoy); or in combination with chemotherapy or cabozantinib (Cabometyx).

The positive opinion is supported by data from the phase 3 CheckMate 67T trial (NCT04810078), which compared subcutaneous nivolumab with intravenous (IV) administration of the drug in patients with pretreated advanced or metastatic clear cell renal cell carcinoma (ccRCC).2

Data presented during the 2024 Genitourinary Cancers Symposium demonstrated that patients who received subcutaneous nivolumab (n = 242) experienced noninferiority in terms of time-averaged serum concentration at day 28 (Cavgd28) vs IV nivolumab (n = 245) with geometric mean Cavgd28of 77.373 μg/mL (90% CI, 74.555-80.297) vs 36.875 μg/mL (90% CI, 35.565-38.235), respectively, translating to a geometric mean ratio of 2.098 (90% CI, 2.001-2.200). Moreover, the geometric mean trough serum concentration at steady state (Cminss) was 122.227 μg/mL (90% CI,114.552-130.416) vs 68.901 μg/mL (90% CI, 64.676-73.402), respectively, for a geometric mean ratio of 1.774 (90% CI, 1.633-1.927).

Additionally, the overall response rate (ORR) by blinded independent central review (BICR) in the subcutaneous arm (n = 248) was 24.2% (95% CI, 19.0%-30.0%) compared with 18.2% (95% CI, 13.6%-23.6%) in the IV arm (n = 247; relative risk, 1.33; 95% CI, 0.94-1.87). Patients achieved a complete response rate of 2.0% vs 1.6%, respectively. The respective disease control rates were 62.9% (95% CI, 56.6%-68.9%) vs 62.8% (95% CI, 56.4%-68.8%) and the median time to response was 3.70 months (95% CI, 1.7-11.1) compared with 3.68 (95% CI, 1.6-11.3). The median progression-free survival by BICR was 7.23 (95% CI, 5.13-7.49) vs 5.65 (95% CI, 5.29-7.39) for the subcutaneous and IV formuations, respectively (HR, 1.06; 0.84-1.34).

“The positive CHMP opinion is an important step forward in the evolution of immuno-oncology and in the potential of subcutaneous [nivolumab] to help transform the lives of people living with cancer,” Dana Walker, MD, MSCE, Opdivo global program lead, Bristol Myers Squibb, stated in a news release.1 “We look forward to bringing the same high-quality care that transformed cancer treatment with an administration method that has the potential to improve the patient experience and efficiency of health care systems in Europe."

CheckMate 67T enrolled patients with advanced or metastatic ccRCC who experienced disease progression during or after treatment with 1 or 2 prior systemic regimens.2 No prior treatment with immune-oncology agents was allowed, and a Karnofsky performance status of at least 70 was required.

Eligible patients were randomly assigned 1:1 to receive subcutaneous nivolumab at 1200 mg plus rHuPH20 every 4 weeks or IV nivolumab at a dose of 3 mg/kg every 2 weeks. Treatment in both arms continued until disease progression, unacceptable toxicity, patient withdrawal, completion of 2 years of treatment, or death.

The coprimary end points for noninferiority testing were Cavgd28 and Cminss. ORR by BICR was the key secondary end point powered for noninferiority testing. Other secondary end points included additional efficacy measures, safety, and pharmacokinetics.

Additional data from CheckMate 67T showed that the safety findings were consistent between subcutaneous and IV nivolumab. Any-grade adverse effects (AEs) occurred at rates of 93.1% vs 93.5%, respectively. Patients in both arms also experienced any-grade treatment-related AEs (TRAEs; 59.1% vs 64.5%), AEs leading to treatment discontinuation (10.1% vs 11.8%), TRAEs leading to treatment discontinuation (4.0% vs 4.9%), serious AEs (SAEs; 27.9% vs 29.0%), and treatment-related SAEs (6.9% vs 6.9%) at similar rates. Three patients died in the subcutaneous arm due to study drug toxicity compared with 1 in the IV arm.

The positive CHMP opinion will be reviewed by the European Commission (EC).1 The EC announces its final decision approximately 2 months after receiving the CHMP opinion; the decision will be applicable to all European Union member states, as well as Iceland, Norway, and Liechtenstein.

References

1. Bristol Myers Squibb receives positive CHMP opinion for the subcutaneous formulation of Opdivo (nivolumab) across multiple solid tumor indications. News release. Bristol Myers Squibb. March 28, 2025. Accessed March 28, 2025. https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Receives-Positive-CHMP-Opinion-for-the-Subcutaneous-Formulation-of-Opdivo-nivolumab-Across-Multiple-Solid-Tumor-Indications/default.aspx
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