October 06, 2025

Published by Maven Regulatory Solutions | September 2025

The U.S. Food and Drug Administration (FDA) has approved a new formulation of pembrolizumab combined with Bera hyaluronidase alfa-pmph (Keytruda Qlex, Merck) for subcutaneous (SC) injection. This approval, announced on September 19, 2025, applies to both adult and pediatric patients (12 years and older) across all solid tumor indications previously approved for the intravenous (IV) formulation of pembrolizumab (Keytruda). This milestone expands access to one of the most widely used immuno-oncology therapies, providing a more convenient administration option for patients and healthcare providers.

Key Highlights of the FDA Approval

  • Product: Pembrolizumab + Bera hyaluronidase alfa-pmph (Keytruda Qlex)
  • Route of Administration: Subcutaneous injection
  • Indications: All FDA-approved IV pembrolizumab solid tumor indications
  • Patient Population: Adults and children ≥12 years
  • Availability: Full prescribing information will be posted on Drugs FDA

Efficacy and Safety Data

The FDA approval is based on Study MK-3475A-D77 (NCT05722015), a randomized, multicenter, open-label, active-controlled trial in patients with treatment-naïve metastatic non-small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 genomic tumor aberrations.

  • Enrollment: 377 patients
  • Treatment Arms:
    • Keytruda Qlex (SC) + platinum doublet chemotherapy
    • IV pembrolizumab + platinum doublet chemotherapy
  • Primary Objective: Pharmacokinetic (PK) comparability
  • PK Endpoints:
  • Cycle 1 AUC0-6 weeks
  • Cycle 3 steady-state Crough
  • Results:
    • Met PK comparability with margins above prespecified threshold (0.8)
    • Confirmed Overall Response Rate (ORR):
      • 45% (SC Keytruda Qlex)
      • 42% (IV pembrolizumab)
    • No notable differences in Progression-Free Survival (PFS) or Overall Survival (OS)

Safety Profile:
  The prescribing information carries warnings for:

  • Immune-mediated adverse reactions
  • Hypersensitivity and administration-related reactions
  • Complications of allogeneic hematopoietic stem cell transplantation
  • Embryo-fetal toxicity

Recommended Dosage

  • Every 3 Weeks: 395 mg pembrolizumab + 4,800 units Bera hyaluronidase alfa-pmph
  • Every 6 Weeks: 790 mg pembrolizumab + 9,600 units Bera hyaluronidase alfa-pmph
  • Continue until disease progression, unacceptable toxicity, or as indicated in prescribing information.

Regulatory & Expedited Programs

This FDA review used Assessment Aid, a voluntary applicant submission that streamlines regulatory evaluation.

The approval aligns with FDA’s ongoing strategy to:

  • Expand oncology drug access
  • Improve patient convenience with subcutaneous immunotherapies
  • Maintain rigorous safety and efficacy standards

Conclusion

The FDA approval of pembrolizumab (Keytruda Qlex) for subcutaneous administration marks a significant advancement in oncology treatment delivery. By providing an alternative to intravenous infusion, this update improves accessibility and treatment experience for patients while maintaining efficacy and safety. Maven Regulatory Solutions continues to monitor and analyze global oncology regulatory updates to support healthcare providers, biopharma innovators, and regulatory professionals in navigating the evolving immunotherapy landscape.