Merck’s KEYTRUDA QLEX Approved in Japan for Subcutaneous Use Across KEYTRUDA Indications
Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) injection for subcutaneous administration across all indications currently approved in Japan for KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy.
The Japanese product is planned to be marketed under the trademark KEYJECT®. The approval introduces a subcutaneous administration option for pembrolizumab that can be delivered by a healthcare professional in as little as one minute, depending on the selected dosing schedule.
KEYJECT can be administered every three weeks in approximately one minute or every six weeks in approximately two minutes. The availability of two administration schedules is intended to provide additional flexibility for patients and healthcare providers as they consider treatment arrangements and appropriate healthcare settings.
Berahyaluronidase alfa, the recombinant hyaluronidase component used with pembrolizumab in the formulation, is a variant of hyaluronidase developed and manufactured by Alteogen Inc.
The Japanese approval represents another regulatory milestone in the development of subcutaneous pembrolizumab and follows approvals in the United States and European Union.
Subcutaneous Option Expands Pembrolizumab Administration
KEYTRUDA has become an established immunotherapy across a broad range of cancers, with pembrolizumab targeting the programmed death receptor-1 (PD-1) pathway. The availability of a subcutaneous formulation provides an alternative to traditional intravenous administration.
For patients receiving long-term cancer treatment, the method and duration of drug administration can be important practical considerations. A subcutaneous injection that can be administered within one or two minutes could potentially reduce the time required for treatment administration compared with conventional infusion-based approaches.
Merck said the Japanese approval is particularly significant because KEYJECT is the first and only subcutaneous immune checkpoint inhibitor available in Japan that can be administered by a healthcare provider in as little as one minute.
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said the approval represents a milestone for patients and healthcare professionals in Japan.
According to Green, the new formulation provides two dosing options and expands choices around where patients can receive their therapy, supporting Merck’s broader focus on patient-centered treatment approaches.
Approval Supported by Phase 3 MK-3475A-D77 Trial
The MHLW approval was supported by results from the pivotal Phase 3 MK-3475A-D77 trial.
The study compared KEYJECT with KEYTRUDA, with both treatments administered every six weeks. The treatments were evaluated in combination with chemotherapy in patients with previously untreated metastatic non-small cell lung cancer (NSCLC) whose tumors did not have EGFR, ALK or ROS1 genomic tumor aberrations.
A key objective of the trial was to compare pharmacokinetic exposure between the subcutaneous and intravenous formulations. The results demonstrated comparable pharmacokinetic exposure levels between KEYJECT and KEYTRUDA.
Pharmacokinetic comparability is an important component in the development of alternative formulations because it helps establish whether the new method of administration produces drug exposure consistent with the established formulation.
The trial also included analyses of clinical outcomes. In descriptive analyses, overall response rates (ORR) were consistent between patients receiving KEYJECT and those receiving KEYTRUDA.
The ORR in the KEYJECT plus chemotherapy group was 45%, with a 95% confidence interval of 39% to 52%. In the KEYTRUDA plus chemotherapy group, the ORR was 42%, with a 95% confidence interval of 33% to 51%.
Merck also reported that there were no notable differences in progression-free survival (PFS) or overall survival (OS) between patients who received KEYJECT and those treated with KEYTRUDA.
These findings provided the clinical and pharmacokinetic evidence supporting the use of the subcutaneous formulation as an alternative administration method for pembrolizumab.
Convenience and Treatment Flexibility
The ability to administer KEYJECT in approximately one or two minutes is a central feature of the newly approved formulation.
Under the Japanese dosing schedules, patients can receive KEYJECT every three weeks through an approximately one-minute administration or every six weeks through an approximately two-minute administration.
The availability of different dosing intervals may give healthcare providers additional flexibility when planning treatment around patients’ clinical needs and treatment schedules.
For patients receiving repeated cancer therapy, treatment administration can form a substantial part of the overall healthcare experience. A shorter administration time may help reduce time spent receiving medication at a healthcare facility, although the overall duration of a patient’s visit will depend on factors such as clinical assessment, chemotherapy administration and other components of care.
The subcutaneous formulation may also offer healthcare professionals another method of delivering pembrolizumab alongside the established intravenous route.
Expanding Access to Subcutaneous Pembrolizumab
The Japanese decision follows regulatory milestones for subcutaneous pembrolizumab in other major markets.
In September 2025, the U.S. Food and Drug Administration (FDA) approved KEYTRUDA QLEX. In the United States, the formulation is approved for adults across the same solid tumor indications as KEYTRUDA.
The European Commission subsequently approved subcutaneous pembrolizumab, marketed as KEYTRUDA SC™ in the European Union, in November 2025. The European formulation is now approved for all KEYTRUDA indications in Europe.
The Japanese approval therefore extends the geographic availability of the subcutaneous formulation and provides another market with an alternative method of administering pembrolizumab.
While the formulation uses the same active immunotherapy, the subcutaneous approach is designed to alter the delivery process rather than introduce a new mechanism of anticancer action.
Role of Berahyaluronidase Alfa
The subcutaneous formulation combines pembrolizumab with berahyaluronidase alfa-pmph.
Berahyaluronidase alfa is a variant of hyaluronidase developed and manufactured by Alteogen Inc. Hyaluronidase-based technologies can facilitate the subcutaneous delivery of medicines by temporarily modifying the extracellular matrix in the injection area, allowing larger volumes or formulations that would otherwise require intravenous administration to be delivered under the skin.
In KEYTRUDA QLEX, this technology supports the development of a subcutaneous version of pembrolizumab.
The formulation provides a different administration route while retaining pembrolizumab as the underlying active immunotherapy.
Potential Impact for Healthcare Providers
The approval also has practical implications for healthcare professionals administering cancer immunotherapy.
Traditional intravenous administration can require infusion-related infrastructure and additional time for drug preparation and administration. A subcutaneous formulation administered in approximately one or two minutes may provide an alternative workflow for appropriate patients and healthcare settings.
However, the choice of administration route will depend on the approved indication, treatment regimen, patient circumstances and healthcare provider judgment.
In patients receiving combination therapies, including chemotherapy, the total treatment process may still involve intravenous administration or other procedures. Consequently, the shorter administration time for pembrolizumab does not necessarily mean that the overall treatment visit will be reduced by the same amount.
Nevertheless, the availability of a rapid subcutaneous administration option expands the range of treatment delivery approaches available to oncology teams.
Broader Development of KEYTRUDA
KEYTRUDA is a PD-1-directed immunotherapy used across multiple cancer types and treatment settings. Its clinical development program has evaluated pembrolizumab across a wide range of solid tumors and hematologic malignancies.
The development of KEYTRUDA QLEX represents an effort to build on the established clinical use of pembrolizumab by introducing an alternative formulation and administration route.
Rather than changing the underlying mechanism of action, the formulation is designed to make pembrolizumab available through subcutaneous injection.
The Phase 3 MK-3475A-D77 results were important in establishing comparable pharmacokinetic exposure between the two formulations. The descriptive response-rate findings and the absence of notable differences in PFS and OS further supported the regulatory evaluation in the studied population.
A New Administration Choice in Japan
The approval of KEYTRUDA QLEX, planned to be marketed as KEYJECT in Japan, provides Japanese healthcare professionals with a subcutaneous option for pembrolizumab across the indications approved for KEYTRUDA in the country.
The formulation can be administered every three weeks in approximately one minute or every six weeks in approximately two minutes. This flexibility could offer additional options for treatment scheduling and administration.
The regulatory decision is supported by Phase 3 evidence demonstrating comparable pharmacokinetic exposure between KEYJECT and KEYTRUDA, alongside consistent descriptive overall response rates and no notable differences in progression-free or overall survival in the studied NSCLC population.
The Japanese approval also follows regulatory authorizations in the United States and European Union, expanding the availability of subcutaneous pembrolizumab internationally.
For Merck, the milestone represents another step in the evolution of KEYTRUDA delivery, while for patients and healthcare providers in Japan, it introduces an additional way to receive and administer an established immunotherapy. As cancer treatment increasingly emphasizes both clinical outcomes and patient-centered care, alternative administration methods such as subcutaneous delivery may become an increasingly important part of treatment planning.
About Study MK-3475A-D77
Study 3475A-D77 is a multicenter, randomized, open-label, active-controlled Phase 3 trial (ClinicalTrials.gov, NCT05722015) conducted in patients with treatment-naïve metastatic non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 genomic tumor aberrations. The primary outcome measure was pembrolizumab exposure [Cycle 1 AUC0-6 weeks and Cycle 3 (i.e. Steady State) Ctrough] of KEYJECT as compared to KEYTRUDA. Additional descriptive efficacy outcome measures were ORR by blinded independent central review (BICR), PFS by BICR and OS. A total of 377 patients were randomized 2:1 to receive either KEYJECT (790 mg/9,600 units) every six weeks with platinum doublet chemotherapy (n=251) or KEYTRUDA (400 mg) every six weeks with platinum doublet chemotherapy (n=126).
About subcutaneous administration
Subcutaneous administration is a method of delivering medications under the skin. Subcutaneous administration may provide added convenience because it offers more options where patients can receive their treatment because it can be administered by healthcare providers in multiple settings from an infusion center to a doctor’s office or a local community-based clinic. For patients who do not require a port or whose veins are difficult to access, subcutaneous administration may simplify treatment administration.
About KEYTRUDA® (pembrolizumab) injection for intravenous use, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 2,800 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
About KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) injection for subcutaneous use, 165 mg + 2,000 units/mL
KEYTRUDA QLEX is a fixed-combination drug product of pembrolizumab and berahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody and berahyaluronidase alfa enhances dispersion and permeability to enable subcutaneous administration of pembrolizumab. KEYTRUDA QLEX is administered as a subcutaneous injection into the thigh or abdomen, avoiding the 5 cm area around the navel, over one minute every three weeks (2.4 mL) or over two minutes every six weeks (4.8 mL).