Subcutaneous Pembrolizumab Approved in EU for All Adult Indications

The European Commission has approved the subcutaneous administration route and pharmaceutical form of pembrolizumab (pembrolizumab and berahyaluronidase alfa; Keytruda SC) for all adult indications of the intravenous (IV) form of pembrolizumab (Keytruda) in the European Union.¹

Comparable efficacy results with subcutaneous pembrolizumab vs IV pembrolizumab in patients with metastatic non–small cell lung cancer (NSCLC) from the phase 3 3475A-D77 trial (NCT05722015) informed the European Commission’s decision. The primary analysis of the trial solidified subcutaneous administration of pembrolizumab (n = 251) as noninferior to pembrolizumab IV (n = 126), with the overall response rate (ORR) in the subcutaneous pembrolizumab arm being 45% (95% Cl, 39%-52%) vs 42% (95% Cl, 33%-51%) in the pembrolizumab IV arm.^1,2 Efficacy results for progression-free survival (PFS) and overall survival (OS) had no differences between patients in each arm of the trial. Furthermore, the geometric mean ratio (GMR) for cycle 1 at AUC_{0-6 weeks} was 1.14 (96% CI, 1.06-1.22; P < .0001), and the GMR for steady-state C_trough was 1.67 (94% CI, 1.52-1.84; P < .0001).²

“We are honored to introduce [subcutaneous pembrolizumab], the first and only subcutaneous immune checkpoint inhibitor in Europe that can be administered in 1 minute every 3 weeks or in 2 minutes every 6 weeks,” Marjorie Green, MD, senior vice president and head of Oncology and Global Clinical Development at Merck Research Laboratories, stated in a news release.¹ “We are committed to discovering patient-focused innovations for people with cancer, like [subcutaneous pembrolizumab], which offers faster administration than [IV pembrolizumab], 2 dosing options, and allows patients more choices of health care settings where they can receive therapy.”

The subcutaneous method of administration implements medications under the skin, enabling administration times that can be as little as 1 minute. The technology offers convenience to patients since they can receive medications through subcutaneous administration in a larger range of settings like community clinics, rather than purely at infusion centers. Moreover, subcutaneous administration offers patients whose veins are hard to access for IV infusion a more accessible method of receiving treatment.

What was the design of the 3475A-D77 study of subcutaneous pembrolizumab in NSCLC?

The multicenter, randomized, open-label trial that compared pembrolizumab through subcutaneous administration vs pembrolizumab through IV infusion enrolled patients who had a histologically or cytologically confirmed diagnosis of squamous or nonsquamous NSCLC and a life expectancy of at least 3 months.³ Patients were at least 18 years of age and were required to provide archival tumor tissue samples or newly obtained biopsies of tumor lesions that were not previously irritated.

If patients had a diagnosis of small cell lung cancer, received prior systemic anticancer therapy for metastatic NSCLC, received prior systemic anticancer therapy including investigational agents within 4 weeks before random assignment, or received prior radiotherapy within 2 weeks of start of study intervention, they were excluded from the study.

Patients in the subcutaneous arm of the trial received 790 mg of pembrolizumab formulated with berahyaluronidase alfa through subcutaneous administration in combination with platinum doublet chemotherapy on day 1 of each 6-week cycle for 18 cycles. Patients in the IV infusion arm of the trial received a 400-mg dose of pembrolizumab through IV infusion in combination with platinum doublet chemotherapy also on day 1 of each 6-week cycle for 18 cycles.^2,3

The trial’s primary objectives were to measure the both the exposure and trough serum concentration of pembrolizumab in each arm to help determine whether subcutaneous administration of the drug was noninferior to IV pembrolizumab. Other secondary objectives of the trial were to evaluate the ORR, PFS, and OS between the 2 arms.

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 20, 2025. https://www.merck.com/news/european-commission-approves-subcutaneous-administration-of-keytruda-pembrolizumab-for-all-adult-indications-approved-in-the-european-union/
2. Felip E, Rojas CI, Schenker M, et al. Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial. Ann Oncol. 2025;36(7):775-785. doi:10.1016/j.annonc.2025.03.012
3. A study of subcutaneous (SC) pembrolizumab coformulated with berahyaluronidase alfa (MK-3475A) vs intravenous pembrolizumab in adult participants with metastatic non-small cell lung cancer (NSCLC) (MK-3475A-D77). ClinincalTrials.gov. Updated September 11, 2025. Accessed November 20, 2025. https://clinicaltrials.gov/study/NCT05722015