Subcutaneous Pembrolizumab Approved in Japan for All Tumor Indications

The Ministry of Health, Labour and Welfare (MHLW) in Japan has approved pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for subcutaneous administration across all indications approved in Japan for intravenous pembrolizumab (Keytruda), according to a news release from Merck.¹ The subcutaneous formulation, which will be marketed in Japan under the planned trademark Keyject, can be administered by a health care provider in as little as 1 minute every 3 weeks or 2 minutes every 6 weeks, making it the first and only subcutaneous immune checkpoint inhibitor available in Japan that can be given in as little as 1 minute.

What supported the Japanese approval of subcutaneous pembrolizumab?

The approval was based on results from the pivotal phase 3 MK-3475A-D77 trial (NCT05722015), which compared subcutaneous pembrolizumab with intravenous pembrolizumab, each administered every 6 weeks in combination with chemotherapy, in patients with treatment-naive metastatic non–small cell lung cancer (NSCLC) with no EGFR, ALK, or ROS1 genomic tumor aberrations. The trial demonstrated comparable pharmacokinetic exposure between the 2 formulations, which was the primary outcome measure. In descriptive efficacy analyses, the objective response rate (ORR) was 45% (95% CI, 39%-52%) in the subcutaneous pembrolizumab plus chemotherapy arm and 42% (95% CI, 33%-51%) in the intravenous pembrolizumab plus chemotherapy arm, with no notable differences in progression-free survival or overall survival between arms.

A total of 377 patients were randomly assigned 2:1 to receive either subcutaneous pembrolizumab at 790 mg/9600 units (n = 251) or intravenous pembrolizumab at (400 mg; n = 126) every 6 weeks, each with platinum-doublet chemotherapy.

“[Subcutaneous pembrolizumab] is the first and only subcutaneous immune checkpoint inhibitor available in Japan that can be administered by a healthcare provider in as little as 1 minute. This approval is a significant milestone for patients and health care providers in Japan and reflects our commitment to advancing new patient-centered care options like [subcutaneous pembrolizumab] that [offer] patients 2 dosing options and more choices of health care settings where they can receive therapy,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in the news release.¹

How is subcutaneous pembrolizumab administered?

Subcutaneous pembrolizumab is a fixed-combination product of pembrolizumab, a PD-1–blocking antibody, and berahyaluronidase alfa, which enhances dispersion and permeability to enable subcutaneous administration. It is administered as a subcutaneous injection into the thigh or abdomen over 1 minute every 3 weeks or over 2 minutes every 6 weeks. Berahyaluronidase alfa is a variant of hyaluronidase developed and manufactured by Alteogen Inc.

What is the global regulatory status of subcutaneous pembrolizumab?

Previously, the FDA approved subcutaneous pembrolizumab and berahyaluronidase alfa-pmph in September 2025 for all solid tumor indications approved for intravenous pembrolizumab in adults based on data from the MK-3475A-D77 trial.² The European Commission subsequently approved the subcutaneous formulation—known as Keytruda SC in the EU—in November 2025 for all pembrolizumab indications in Europe.

What are the potential benefits of subcutaneous administration?

Subcutaneous administration delivers medication under the skin and may offer added convenience by expanding the settings in which patients can receive treatment, including infusion centers, physician offices, and community-based clinics. For patients who do not require a port or whose veins are difficult to access, subcutaneous administration may simplify treatment delivery. The subcutaneous formulation provides 2 dosing options, every 3 weeks or every 6 weeks, for eligible patients.

References

1. Merck’s Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) approved in Japan for subcutaneous administration for all Keytruda (pembrolizumab) indications approved in Japan. News release. Merck. September 21, 2026. Accessed September 23, 2026. https://tinyurl.com/4dexff72
2. FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. News release. FDA. September 19, 2025. Accessed September 23, 2026. https://tinyurl.com/4ns5e8j7