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FDA approves subcutaneous pembrolizumab for solid tumors

On September 19, 2025, the U.S. Food and Drug Administration (FDA) granted approval to subcutaneous (SC) administration of pembrolizumab, together with berahyaluronidase alfa (MK-3475A; from now on referred to as SC pembrolizumab), for the first-line treatment of adult patients with solid tumors previously approved in pembrolizumab.1 SC administration of therapeutic agents has been shown to have advantages over intravenous (IV) administration, such as higher patient satisfaction and lower emotional burden2.

The FDA approval was supported by the pivotal Phase III 3475A-D77 trial (NCT05722015), a randomized, open-label study, which evaluated the efficacy and safety of SC pembrolizumab versus IV pembrolizumab, administered with chemotherapy, in 377 patients with non-small cell lung cancer (NSCLC). The study met its primary endpoint, demonstrating noninferior pharmacokinetics (PK). SC pembrolizumab, administered every six weeks, with a mean injection time of 2 minutes plus chemotherapy, achieved a geometric mean ratio for area under the curve (AUC) of 1.14 (96% CI, 1.06–1.22). For trough concentration (Ctrough), the geometric mean ratio was 1.67 (94% CI, 1.52–1.84) at steady state, compared to IV pembrolizumab every 6 weeks with chemotherapy.3

The key secondary endpoints of the trial were also comparable. The objective response rate (ORR) was 45.4% (95% CI, 39.1–51.8) with SC pembrolizumab vs 42.1% (95% CI, 33.3–51.2) with IV. Median progression-free survival (PFS) was 8.1 months vs 7.8 months (HR, 1.05; 95% CI, 0.78–1.43), and median duration of response (DOR) was 9.1 months vs 8.0 months. Median overall survival (OS) was not reached in either arm (HR, 0.81; 95% CI, 0.53–1.22). Safety profiles were consistent, with similar rates of grade 3 or greater adverse events (AEs) observed in both arms (47% for SC vs 47.6% for IV).3

These findings support the administration of SC pembrolizumab across all indications where IV pembrolizumab is currently used. The SC pembrolizumab regimen may offer greater flexibility, particularly in early-stage settings, and has the potential to both improve patient satisfaction and reduce time demands in the clinic.

References:

  1. Center for Drug Evaluation and Research. FDA approves pembrolizumab and berahyaluronidase alfa-pmph [Internet]. U.S. Food and Drug Administration. 2025 [cited 2025 Sep 19]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-and-berahyaluronidase-alfa-pmph-subcutaneous-injection
  2. George S, Bourlon MT, Overman MJ, Dixon M, Shelley K, Markus KJ, et al. Systematic literature review of intravenous versus subcutaneous administration of oncology therapies: A clinical, economic and patient perspective. Cancer Treatment Reviews. 2025 Jun;102974.
  3. Felip E, Rojas CI, Schenker M, Kowalski DM, Casarini IA, Csöszi T, 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. Annals of Oncology. 2025 Mar 27