Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved subcutaneous pembrolizumab and berahyaluronidase alfa for subcutaneous administration across all indications for which intravenous pembrolizumab is currently approved in Japan.
The approval introduces the first and only subcutaneous immune checkpoint inhibitor available in Japan, according to Merck, offering an alternative to intravenous administration that can be delivered by a healthcare professional in as little as one minute.
The subcutaneous formulation can be administered in approximately one minute every three weeks or two minutes every six weeks. It combines pembrolizumab with berahyaluronidase alfa, a variant of hyaluronidase developed and manufactured by Alteogen that enables the subcutaneous delivery of pembrolizumab.
Subcutaneous Pembrolizumab Offers a New Administration Option
Pembrolizumab is a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1). By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, pembrolizumab activates T lymphocytes that may affect tumor cells.
Berahyaluronidase alfa enhances dispersion and permeability, allowing pembrolizumab to be administered subcutaneously rather than through intravenous infusion.
The formulation is administered as a subcutaneous injection into the thigh or abdomen. Administration takes approximately one minute every three weeks or two minutes every six weeks.
Subcutaneous administration may provide patients and healthcare providers with greater flexibility regarding where treatment can be delivered, including infusion centers, physicians’ offices, and community-based clinics. For patients who do not require a port or have difficult venous access, it may also simplify treatment administration.
Marjorie Green, MD, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, described the approval as an important development for patients and healthcare providers in Japan, saying:
“This approval is a significant milestone for patients and healthcare providers in Japan.”
Green added that the approval reflects the company’s efforts to advance patient-centered treatment options, including additional dosing options and greater choice in healthcare settings where therapy can be administered.
Phase 3 MK-3475A-D77 Trial Supported the Approval
The approval was based on findings from the pivotal Phase 3 MK-3475A-D77 trial (NCT05722015), a multicenter, randomized, open-label, active-controlled study comparing subcutaneous pembrolizumab plus berahyaluronidase alfa with intravenous pembrolizumab.
The study enrolled 377 patients with previously untreated metastatic non-small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 genomic tumor aberrations.
Patients were randomized 2:1 to receive either subcutaneous pembrolizumab plus berahyaluronidase alfa at 790 mg/9,600 units every six weeks with platinum-doublet chemotherapy (n=251) or intravenous pembrolizumab at 400 mg every six weeks with platinum-doublet chemotherapy (n=126).
The primary outcome assessed pembrolizumab exposure, including Cycle 1 AUC0–6 weeks and Cycle 3 steady-state trough concentration.
The trial demonstrated comparable pharmacokinetic exposure between subcutaneous and intravenous pembrolizumab.
Response Rates Consistent With Intravenous Pembrolizumab
Descriptive efficacy analyses also showed generally consistent outcomes between the two treatment groups.
The overall response rate was 45% (95% CI, 39–52) among patients receiving subcutaneous pembrolizumab plus berahyaluronidase alfa with chemotherapy, compared with 42% (95% CI, 33–51) among those receiving intravenous pembrolizumab with chemotherapy.
According to Merck, there were also no notable differences in progression-free survival or overall survival between patients receiving the subcutaneous and intravenous formulations.
Subcutaneous Pembrolizumab Expands Globally
The Japanese authorization follows regulatory approvals of subcutaneous pembrolizumab in other major markets.
In September 2025, the U.S. Food and Drug Administration approved the fixed combination of pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous administration in adults across the same solid tumor indications as intravenous pembrolizumab.
The European Commission subsequently approved subcutaneous pembrolizumab in November 2025, covering all indications for which pembrolizumab is approved in Europe.
With the latest authorization, patients eligible for pembrolizumab across its approved indications in Japan now have access to a subcutaneous option that can be administered in as little as one minute, offering an alternative to traditional intravenous delivery.
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