On September 19, 2025, the Food and Drug Administration approved pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection for adult and paediatric (12 years and older) solid tumour indications approved for the intravenous formulation of pembrolizumab. See the prescribing information for the specific indications.

Full prescribing information for pembrolizumab and berahyaluronidase alfa-pmph will be posted on Drugs@FDA. 

Efficacy and Safety

Efficacy was evaluated in Study MK-3475A-D77 (NCT05722015), a randomised, multicenter, open-label, active-controlled trial conducted in patients with treatment-naïve metastatic non-small cell lung cancer (NSCLC), in whom there were no EGFR, ALK, or ROS1 genomic tumour aberrations. A total of 377 patients were randomised (2:1) to receive either pembrolizumab and berahyaluronidase alfa-pmph administered subcutaneously every six weeks with platinum doublet chemotherapy or pembrolizumab administered intravenously every six weeks with platinum doublet chemotherapy.

The primary objective was to assess the exposure of subcutaneous pembrolizumab and berahyaluronidase alfa-pmph compared to intravenous pembrolizumab, with dual primary pharmacokinetic (PK) endpoints of Cycle 1 AUC0-6 weeks and Cycle 3 (i.e., Steady State) Ctrough.

Descriptive efficacy outcome measures were overall response rate (ORR) by blinded independent central review (BICR), progression-free survival (PFS) by BICR, and overall survival (OS). The trial met the predefined acceptance margin for the PK endpoints with the lower boundary (96% CI for Cycle 1 AUC0-6weeks and 94% CI for Cycle 3 Ctrough) of the geometric mean ratios 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. There were no notable differences in PFS or OS observed in patients who received pembrolizumab and berahyaluronidase alfa-pmph compared to patients who received intravenous pembrolizumab.

The prescribing information includes warnings and precautions for immune-mediated adverse reactions, hypersensitivity and administration-related reactions, complications of allogeneic haematopoietic stem cell transplantation, and embryo-fetal toxicity.

Source: FDA