SUMMARY: The FDA on September 19, 2025 approved Pembrolizumab and berahyaluronidase alfa-pmph (KEYTRUDA QLEX®) for subcutaneous injection for adult and pediatric (12 years and older) solid tumor indications, approved for the intravenous formulation of Pembrolizumab (KEYTRUDA®).
KEYTRUDA® is a fully humanized, Immunoglobulin G4, monoclonal antibody and checkpoint inhibitor, that binds to the PD-1 receptor and blocks its interaction with ligands PD-L1 and PD-L2, thereby undoing PD-1 pathway-mediated inhibition of the immune response and unleashing the tumor-specific effector T cells.
KEYTRUDA QLEX® is a fixed-dose combination of Pembrolizumab and Berahyaluronidase alfa, a recombinant variant of human hyaluronidase that enhances drug dispersion and absorption to enable subcutaneous delivery.
Clinical Evidence Supporting Approval
The regulatory decision was based on results from the MK-3475A-D77 trial (NCT05722015), a randomized, open-label, multicenter Phase 3 study in treatment-naïve metastatic Non–Small Cell Lung Cancer (NSCLC) without EGFR, ALK, or ROS1 alterations.
- Design: 377 patients were randomized 2:1 to receive either subcutaneous KEYTRUDA QLEX® (790 mg/9,600 units) plus platinum doublet chemotherapy every six weeks (N=251) or KEYTRUDA® 400 mg IV plus platinum doublet chemotherapy every six weeks (N=126).
- Primary Objective: Pharmacokinetic (PK) comparability, with dual endpoints of Cycle 1 AUC 0-6 weeks and Cycle 3 steady-state trough concentration (C trough).
- Descriptive Outcomes: Objective Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS) assessed by Blinded Independent Central Review (BICR).
Key findings:
- The PK exposure of subcutaneous KEYTRUDA QLEX® met predefined comparability criteria, with geometric mean ratios exceeding the prespecified threshold of 0.8.
- Confirmed ORR was 45.4% with KEYTRUDA QLEX® versus 42.1% with IV KEYTRUDA® (ORR ratio 1.08, 95% CI 0.85-1.37)
- No clinically meaningful differences were observed in PFS or OS between the two treatment groups.
- Safety profile was consistent with IV KEYTRUDA®. The most common adverse reactions (≥20%) with KEYTRUDA QLEX® plus chemotherapy included nausea (25%), fatigue (25%), and musculoskeletal pain (21%).
Clinical and Practical Implications
While the pivotal data were generated in NSCLC, the FDA approval extends to all solid tumor indications where KEYTRUDA® is currently approved, offering oncologists a new delivery option across a broad spectrum of cancers.
The subcutaneous formulation provides substantial administration advantages:
- Time savings: injection takes ~1–2 minutes versus ~30 minutes for IV infusion.
- Patient convenience: fewer logistical barriers, particularly relevant for patients requiring long-term therapy.
- System efficiency: reduced chair time and preparation burden for healthcare providers.
The approved dosing schedules are:
- KEYTRUDA QLEX® 395 mg/4,800 units SQ every 3 weeks, or
- KEYTRUDA QLEX® 790 mg/9,600 units SQ every 6 weeks,
continued until disease progression, unacceptable toxicity, or as otherwise specified in the prescribing information.
Takeaway for Practice
The approval of KEYTRUDA QLEX® represents an important advancement in immuno-oncology care delivery. By maintaining clinical efficacy and safety while significantly streamlining treatment administration, this new formulation has the potential to improve both the patient experience and healthcare system efficiency. For busy oncology practices, it provides a practical alternative to infusion without compromising the therapeutic benefits of KEYTRUDA®.
Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial. Felip E, Rojas CI, Schenker M, et al. Ann Oncol. 2025;36:775-785.
