Clinical Trial Data With Subcutaneous Pembrolizumab

Subcutaneous pembrolizumab received FDA approval based on phase 3 trial MK-3475A-D77, evaluating subcutaneous formulation combined with berahyaluronidase (a different hyaluronidase than used with nivolumab) vs intravenous (IV) pembrolizumab in patients with treatment-naive metastatic non–small cell lung cancer. The trial randomly assigned patients 2:1 to receive subcutaneous pembrolizumab every 6 weeks with platinum doublet chemotherapy or standard IV pembrolizumab with chemotherapy. The subcutaneous formulation involves approximately 5 mL administered over slightly more than 2 minutes, representing one of the smaller injection volumes among approved subcutaneous immune checkpoint inhibitors.

Pharmacokinetic comparability was established through primary end points measuring cycle 1 drug exposure (area under curve, 0-6 weeks) and cycle 3 steady-state concentration, with geometric mean ratio lower boundaries exceeding the 0.8 threshold. Secondary efficacy end points evaluated by blinded independent central review showed comparable results, with overall response rates of 40% for subcutaneous vs 42% for IV administration, and no meaningful differences in progression-free survival or overall survival. The safety profile remained consistent with IV pembrolizumab, supporting the pattern that subcutaneous formulations maintain established safety characteristics without introducing new concerning signals.

Dosing schedules for subcutaneous pembrolizumab follow indication-specific regimens: 395 mg pembrolizumab with 4800 units berahyaluronidase every 3 weeks, or 790 mg pembrolizumab with 9600 units berahyaluronidase every 6 weeks. The variability in administration times (ranging from 2 to 7 minutes across different subcutaneous products), injection volumes, and specific protocols highlights an opportunity for standardization that could enhance staff experience and adoption. Health care providers suggest developing standardized subcutaneous administration rates based on injection volume ranges (for example, 1 minute for volumes under 5 mL, 2-3 minutes for 5-10 mL) to simplify training and reduce the complexity of remembering product-specific requirements while maintaining safety.