FDA Approves SC Pembrolizumab Formulation in Solid Tumors

The FDA approved subcutaneous pembrolizumab based on prior data from Study MK-3475A-D77 (NCT05722015).

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