European Commission approves subcutaneous pembrolizumab

The European Commission (EC) has approved a subcutaneous formulation of pembrolizumab and berahyaluronidase alfa-pmph (Keytruda SC in Europe; Keytruda QLEX in the US) across all 33 previously approved adult indications for pembrolizumab in Europe.¹

This decision is valid in all 27 European Union member states as well as in Iceland, Liechtenstein, and Norway. The approval follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use in September 2025.

The subcutaneous formulation of pembrolizumab also received FDA approval in September 2025.²

“We are honored to introduce KEYTRUDA SC, the first and only subcutaneous immune checkpoint inhibitor in Europe that can be administered in one minute every three weeks or in two minutes every six weeks,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in a news release from the company.¹ “We are committed to discovering patient-focused innovations for people with cancer like KEYTRUDA SC, which offers faster administration than KEYTRUDA, two dosing options and allows patients more choices of health care settings where they can receive therapy.”

The EC approval is supported by data from the phase 3 3475A-D77 trial (NCT05722015), in which the subcutaneous formulation of pembrolizumab demonstrated noninferior pharmacokinetics (PK) compared with the intravenous (IV) formulation in patients with treatment-naive metastatic non–small cell lung cancer (NSCLC).

In total, the open-label, multicenter 3475A-D77 trial enrolled 377 patients with NSCLC with no EGFR, ALK, or ROS1 genomic tumor aberrations.Participants were randomly assigned 2:1 to receive either subcutaneous pembrolizumab (790 mg/9600 units) every 6 weeks in combination with chemotherapy (n = 251) or IV pembrolizumab (400 mg) every 6 weeks with chemotherapy (n = 126). The dual primary end points for the study were cycle 1 area under the curve (AUC) and steady-state trough concentration (Ctrough) at cycle 3.

Overall, subcutaneous pembrolizumab demonstrated noninferior AUC exposure during the first dosing cycle, with a geometric mean ratio of 1.14 (96% CI, 1.06 to 1.22; P < .0001).³ The subcutaneous formulation also showed noninferiority compared with the IV formulation in steady-state trough concentration, with a geometric mean ratio of 1.67 (94% CI, 1.52 to 1.84; P < .0001).

Secondary efficacy end points were also comparable between both arms. Overall, the objective response rate was 45.4% (95% CI, 39.1 to 51.8) with the subcutaneous formulation vs 42.1% (95% CI, 33.3 to 51.2) with the IV formulation. The median duration of response was 9.1 months (95% CI, 6.9 to not reached [NR]) in the subcutaneous arm vs 8.0 months (95% CI, 7.4 to NR) in the IV arm.

Both progression-free survival (PFS) and overall survival (OS) were also comparable. Specifically, the median PFS was 8.1 months (95% CI, 6.3 to 8.3) in the subcutaneous arm vs 7.8 months (95% CI, 6.2 to 9.7) in the IV arm (HR, 1.05; 95% CI, 0.78 to 1.43). The median OS was not reached in either arm (HR, 0.81; 95% CI, 0.53 to 1.22).

Notably, the median injection time for subcutaneous pembrolizumab (4.8 mL) was 2 minutes. In the phase 3 study, the subcutaneous formulation reduced the time for patients spent in chair and in the treatment room by 49.7% and 47.4%, respectively. The subcutaneous formulation also reduced the total active time spent by health care professionals on treatment preparation, administration process, and patient monitoring by 45.7%.

Grade 3 or higher adverse events (AEs) were reported in 47% of patients in the subcutaneous arm vs 47.6% of patients in the IV arm. The most common AEs in patients who received subcutaneous pembrolizumab included nausea (25%), fatigue (25%), and musculoskeletal pain (21%).

REFERENCES

1. European Commission approves subcutaneous administration of KEYTRUDA® (pembrolizumab) for all adult indications approved in the European Union. News release. Merck. November 19, 2025. Accessed November 19, 2025. https://www.merck.com/news/european-commission-approves-subcutaneous-administration-of-keytruda-pembrolizumab-for-all-adult-indications-approved-in-the-european-union/

2. FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. FDA. September 19, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-and-berahyaluronidase-alfa-pmph-subcutaneous-injection

3. Merck’s investigational subcutaneous pembrolizumab with berahyaluronidase alfa demonstrates noninferior pharmacokinetics compared to intravenous (IV) KEYTRUDA (pembrolizumab) in pivotal 3475A-D77 trial. News release. Merck. March 27, 2025. Accessed November 19, 2025. https://www.merck.com/news/mercks-investigational-subcutaneous-pembrolizumab-with-berahyaluronidase-alfa-demonstrates-noninferior-pharmacokinetics-compared-to-intravenous-iv-keytruda-pembrolizumab-in-pivotal/