FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection
Regulatory approval: On Sept 19, 2025, the FDA approved pembrolizumab and berahyaluronidase alfa‑pmph (Keytruda Qlex, Merck) for subcutaneous injection for adult and pediatric patients (≥12 years) across solid-tumor indications already approved for IV pembrolizumab; clinicians are directed to the prescribing information for indication specifics. Approval was supported by PK comparability data and descriptive efficacy outcomes from MK‑3475A‑D77 in treatment‑naïve metastatic NSCLC without EGFR/ALK/ROS1 aberrations.
FDA approval: subcutaneous pembrolizumab/berahyaluronidase (Keytruda Qlex)
Type: Regulatory approval
Date: 2025-09-19
Agency: FDA
On September 19, 2025, the FDA approved pembrolizumab and berahyaluronidase alfa‑pmph (Keytruda Qlex, Merck) for subcutaneous injection for adult and pediatric patients (12 years and older) with solid tumor indications that are already approved for the intravenous (IV) formulation of pembrolizumab (Keytruda). The FDA noted to see the prescribing information for the specific indications; full prescribing information is expected to be posted on Drugs@FDA.
Supporting evidence
Efficacy and safety were evaluated in MK‑3475A‑D77 (NCT05722015), a randomized, multicenter, open-label, active-controlled trial in treatment‑naïve metastatic NSCLC with no EGFR, ALK, or ROS1 genomic tumor aberrations (N=377; 2:1 randomization). Patients received either subcutaneous Keytruda Qlex q6w + platinum doublet chemotherapy or IV pembrolizumab q6w + platinum doublet chemotherapy.
The primary objective assessed exposure comparability, with dual PK endpoints (Cycle 1 AUC0–6 weeks and Cycle 3 steady-state Ctrough). The trial met predefined acceptance margins; the lower boundaries of geometric mean ratio CIs (96% for Cycle 1 AUC and 94% for Cycle 3 Ctrough) were above the prespecified threshold (0.8). Confirmed ORR was 45% (95% CI 39–52) for subcutaneous vs 42% (95% CI 33–51) for IV; no notable differences in PFS or OS were observed.
Dosing and safety highlights
Recommended dosing: 395 mg pembrolizumab + 4,800 units berahyaluronidase q3w or 790 mg + 9,600 units q6w, per labeling. Labeling includes warnings/precautions for immune-mediated adverse reactions, hypersensitivity/administration-related reactions, allogeneic HSCT complications, and embryo-fetal toxicity.