FDA Approves SC Pembrolizumab Formulation in Solid Tumors

The FDA has approved a subcutaneous injection of pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for all solid tumor indications approved for intravenous pembrolizumab (Keytruda) as treatment for adult and pediatric patients, according to a news release from the FDA.¹

Supporting results came from the randomized, active-controlled phase 3 MK-3475A-D77 trial (NCT05722015) evaluating subcutaneous pembrolizumab vs intravenous pembrolizumab administered every 6 weeks, both with chemotherapy, in patients with treatment-naïve metastatic non–small cell lung cancer (NSCLC). Primary results from the trial were published in Annals of Oncology.²

It was found that both the overall exposure, as well as the trough concentration levels, of subcutaneous pembrolizumab at 790 mg once every 6 weeks were noninferior to intravenous pembrolizumab at 400 mg every 6 weeks.

The confirmed overall response rate (ORR) with the subcutaneous treatment was 45% (95% CI, 39%-52%) compared with 42% (95% CI, 33%-51%) in the intravenous pembrolizumab arm. Furthermore, no notable differences were observed for progression-free survival, with median values of 8.1 months (95% CI, 6.3-8.3) and 7.8 months (95% CI, 6.2-9.7), respectively, or overall survival (OS), with OS event rates of 24.3% and 29.4%.

Treatment with the subcutaneous formulation is recommended at 2 dose levels; the first is 395 mg of pembrolizumab and 4800 units of berahyaluronidase alfa-pmph every 3 weeks, or 790 mg of pembrolizumab and 9600 units of berahyaluronidase alfa-pmph every 6 weeks. Treatment should continue until disease progression or unacceptable toxicity.

Overall, 377 patients were randomly assigned, in a 2:1 ratio, to receive either the subcutaneous treatment administered every 6 weeks with platinum doublet chemotherapy or pembrolizumab administered intravenously every 6 weeks with platinum doublet chemotherapy.

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

References

1. FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. Release. FDA. September 19, 2025. Accessed September 19, 2025. https://tinyurl.com/4ns5e8j7
2. 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