EMA Validates Application for Subcutaneous Nivolumab in Solid Tumors

Supporting findings for the application came from the phase 3 CheckMate-67T trial (NCT04810078) evaluating subcutaneous nivolumab compared with intravenous therapy among patients with previously treated advanced or metastatic clear cell renal cell carcinoma.

The European Medicines Agency (EMA) has validated an extension application for subcutaneous nivolumab (Opdivo) and hyaluronidase (rHuPH20) for multiple solid tumor types in adult patients, according to a press release from the developers, Bristol Myers Squibb.¹

Specifically, the subcutaneous formulation would be intended for use as monotherapy, as monotherapy maintenance after prior treatment with nivolumab plus ipilimumab (Yervoy), or as part of a regimen including chemotherapy or cabozantinib (Cabometyx). With the EMA validating this extension application, the agency will now begin a centralized review process to decide on approving subcutaneous nivolumab.

“Subcutaneous nivolumab has the potential to change the way patients living with cancer receive [nivolumab] treatment and to significantly reduce administration time by utilizing a single injection in 3-to-5 minutes. By providing patients the same quality of care as [intravenous nivolumab] in a fraction of the time, patients can focus on what is important to them rather than spending a longer wait time at the infusion center,” Susan Parker, vice president and global program lead of Product Design & Development at Bristol Myers Squibb, said in the press release.¹ “We look forward to working with the EMA to advance this application with the goal of introducing the subcutaneous option of [nivolumab].”

Supporting findings for the application came from the phase 3 CheckMate-67T trial (NCT04810078) evaluating subcutaneous nivolumab compared with intravenous therapy among patients with previously treated advanced or metastatic clear cell renal cell carcinoma (RCC). Investigators previously highlighted results from the CheckMate-67T trial at the 2024 Genitourinary Cancers Symposium.²

Data showed that the co-primary pharmacokinetic end points for demonstrating the inferiority of subcutaneous nivolumab vs intravenous therapy were met. Additionally, subcutaneous treatment demonstrated noninferiority in the key secondary end point of objective response rate (ORR) per blinded independent central review (BICR). The ORR was 24.2% (95% CI, 19.0%-30.0%) in the subcutaneous arm vs 18.2% (95% CI, 13.6%-23.6%) in the intravenous arm (relative risk [RR], 1.33; 95% CI, 0.94-1.87).

The disease control rate (DCR) was 62.9% (95% CI, 56.6%-68.9%) with subcutaneous therapy vs 62.8% (95% CI, 56.4%-68.8%) with intravenous treatment (risk ratio, 1.01; 95% CI, 0.88-1.15). Additionally, the median progression-free survival (PFS) was 7.23 months (95% CI, 5.13-7.49) vs 5.65 (95% CI, 5.29-7.39) in each respective arm (HR, 1.06; 95% CI, 0.84-1.34).

In the subcutaneous and intravenous nivolumab arms, respectively, investigators reported grade 3/4 adverse effects (AEs; 35.2% vs 40.8%), treatment-related AEs (TRAEs; 9.7% vs 14.7%), serious AEs (21.1% vs 22.9%), and AEs resulting in treatment discontinuation (7.3% vs 8.6%). Common any-grade AEs in each respective arm included arthralgia (11.7% vs 15.9%), fatigue (7.7% vs 15.9%), diarrhea (9.7% vs 13.5%), and hyperglycemia (9.3% vs 13.1%).

In the CheckMate-67T trial, patients were assigned 1:1 to receive nivolumab subcutaneously at 1200 mg plus rHuPH20 every 4 weeks (n = 248) or nivolumab intravenously at 3 mg/kg every 2 weeks (n = 247).

The trial’s co-primary end points were C_avgd28 and C_minss in the subcutaneous and intravenous therapy arms. Secondary end points included the incidence of anti-nivolumab antibodies and neutralizing antibodies following treatment.

Patients with advanced or metastatic clear cell RCC and disease progression on or after 1 or 2 prior lines of systemic therapy were eligible for enrollment on the trial. Having a Karnofsky performance status of 70 or higher was another requirement for study entry.

The FDA accepted a biologics license application for subcutaneous nivolumab plus rHuPH20 across all previous solid tumor indications for which intravenous nivolumab already received approval for in May 2024.³ Data from the CheckMate-67T trial supported the application submitted to the FDA.

References

1. European Medicines Agency validates Bristol Myers Squibb’s application for subcutaneous nivolumab. News release. Bristol Myers Squibb. June 21, 2024. Accessed June 21, 2024. https://tinyurl.com/yh8s649b
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. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed June 21, 2024. https://bit.ly/3JL8yY1