FDA Approves Subcutaneous Pembrolizumab for Solid Tumor Indications

The FDA has approved the biologics license application (BLA) for the subcutaneous (SC) administration of pembrolizumab (Keytruda Qlex) formulated with berahyaluronidase alfa (MK-3475A) across all previously approved solid tumor indications for pembrolizumab, including metastatic nonsquamous non–small cell lung cancer (NSCLC).¹

The decision comes after results of the pivotal phase 3 3475A-D77 trial (NCT05722015) demonstrated noninferior pharmacokinetics (PK) of SC pembrolizumab compared with intravenous (IV) pembrolizumab when combined with chemotherapy in first-line treatment of metastatic NSCLC, meeting its dual primary end points.²

The phase 3 347A-D77 study is a global, randomized, open-label trial assessing PK of SC pembrolizumab formulated with berahyaluronidase alfa compared with IV pembrolizumab in combination with chemotherapy. The study’s primary end points are area under the curve (AUC) of pembrolizumab exposure and model-based trough serum concentration (C_trough) of pembrolizumab measured at steady state. The study met these end points with an AUC geometric mean ratio (GMR) of 1.14 (96% CI, 1.06–1.22)and C_trough GMR of 1.67 (94% CI, 1.52–1.84).³

Regarding response, the objective response rate (ORR) was 45.4% (95% CI, 39.1%–51.8%) in the SC pembrolizumab arm compared with 42.1% (95% CI, 33.3%–51.2%) in the IV pembrolizumab arm. The median duration of response (DOR) was 9.1 months (95% CI, 6.9–not reached) with SC pembrolizumab compared with 8.0 months (95% CI, 7.4–not reached) with IV pembrolizumab. The median progression-free survival (PFS) was 8.1 months (95% CI, 6.3–8.3) with SC pembrolizumab compared with 7.8 months (95% CI, 6.2–9.7) with IV pembrolizumab. Median overall survival (OS) was not reached in either arm.³

Regarding safety, SC pembrolizumab demonstrated consistent safety profiles with IV pembrolizumab, with similar rates of treatment-related adverse events (TRAEs), grade 3 to grade 5 TRAEs, and serious TRAEs between arms.³ TRAEs resulted in discontinuation among 8.4% of patients receiving SC pembrolizumab and 8.7% of patients receiving IV pembrolizumab.

The study enrolled 377 patients with histologically or cytologically confirmed, squamous or nonsquamous NSCLC,⁴ randomized 2:1 to receive either SC pembrolizumab every 6 weeks with a median injection time of 2 minutes (4.8 mL) plus chemotherapy (n = 251) or IV pembrolizumab every 6 weeks with chemotherapy (n = 126).³

Of note, an observational, prospective time and motion study derived from the 3475A-D77 trial also found that the experimental treatment significantly reduced patients’ time in-chair and in the treatment room by 49.7% and 47.4%, respectively, and health care practitioners’ total active time by 45.7% including time spent on preparation, administration, and patient monitoring, compared to IV pembrolizumab (P <.0001). These findings highlight SC pembrolizumab’s potential to improve the care experience for patients and health care practitioners alike.²

REFERENCES:

1. FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. News release. US FDA. September 19, 2025. Accessed September 19, 2025. https://tinyurl.com/2n3rsmjz

2. Merck’s Investigational Subcutaneous Pembrolizumab With Berahyaluronidase Alfa Demonstrates Noninferior Pharmacokinetics Compared to Intravenous (IV) KEYTRUDA® (pembrolizumab) in Pivotal 3475A-D77 Trial. News release. Merck. Published March 27, 2025. Accessed September 12, 2025. https://tinyurl.com/43w723rj

3. 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:https://doi.org/10.1016/j.annonc.2025.03.012

4. A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77). ClinicalTrials.gov. Updated September 11, 2025. Accessed September 14, 2025. https://clinicaltrials.gov/study/NCT03083873