On September 19, the US Food and Drug Administration (FDA) approved pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection for solid tumor indications in which intravenous pembrolizumab is accepted. This is for individuals 12 and older.¹

This approval is based on results from a phase III randomized, multicenter, open-label, active-controlled MK-3475A-D77 study, which was conducted in 377 patients with previously untreated non-small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 alterations. Patients were randomly assigned (2:1) to receive either pembrolizumab and berahyaluronidase alfa-pmph subcutaneously every 6 weeks with chemotherapy or intravenous pembrolizumab, along with chemotherapy.²

The trial included dual primary endpoints of pharmacokinetic (PK) exposure measures of cycle 1 (AUC 0-6 weeks) and cycle 3 steady-state trough concentration (Ctrough) of pembrolizumab.Secondary endpoints included additional PK exposure measures, pembrolizumab immunogenicity, efficacy, and safety.²  Descriptive efficacy outcome measures were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).¹

The trial met the predefined acceptance margin for the PK endpoints with the lower boundary (96% confidence interval [CI] for cycle 1 AUC 0-6 weeksand 94% CI for cycle 3 Ctrough) of the geometric mean ratios (GMR) above the pre-specified threshold of 0.8 for comparability. The confirmed ORR was 45% (95% CI: 39, 52) in the subcutaneous pembrolizumab and berahyaluronidase alfa-pmph arm, and 42% (95% CI: 33, 51) in the intravenous pembrolizumab arm.¹

Response rates were comparable between subcutaneous (45%) and intravenous (42%) routes, with no significant difference. These routes resulted in similar PFS and OS rates among patients.¹

References:

• FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection
• 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