FDA Approves Subcutaneous Pembrolizumab for Patients With Solid Tumors
On September 19th, 2025, the US Food and Drug Administration (FDA) approved subcutaneous pembrolizumab plus berahylaruonidase alfa-pmph for adult and pediatric patients (12 years of age and older) with solid tumors eligible to receive intravenous pembrolizumab. This approval was based on results from the MK-3475A-D77 trial.
In this multicenter, open-label, active-controlled trial, 377 treatment-naive patients with metastatic non-small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 alterations were randomized on a 2-to-1 basis to receive either subcutaneous pembrolizumab plus berahylaruonidase alfa, or intravenous pembrolizumab once every 6 weeks with platinum doublet chemotherapy. The primary end point was subcutaneous exposure with dual primary pharmacokinetic end points of Cycle 1 AUC0-6 weeks and Cycle 3 Ctrough. Efficacy end points included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), by blinded independent central review.
At analysis, the trial met the predefined acceptance margin for pharmacokinetic end points with the lower boundary of the genomic mean ratios of 96% for Cycle 1 AUC0-6 weeks and 94% Cycle 3 Ctrough, both above the pre-specified threshold of 0.8. The confirmed ORR was 45% in the subcutaneous arm and 42% in the intravenous arm. No significant difference in PFS or OS was observed.
The recommended dose is either 395 mg of pembrolizumab plus 4800 units of berahylaruonidase alfa every 3 weeks, or 790 mg of pembrolizumab plus 9600 units of berahylaruonidase alfa every 6 weeks until disease progression or unacceptable toxicity.
Prescribing information includes warnings and precautions for immune-mediated adverse reactions, hypersensitivity and administration-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Source:
FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. Accessed on September 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-and-berahyaluronidase-alfa-pmph-subcutaneous-injection
