Merck's Subcutaneous Keytruda (Pembrolizumab) Becomes First PD-1 Antibody of Its Kind to File for Approval in China

On June 7, the CDE website showed that MSD had submitted a PD-1 inhibitor in China.Pembrolizumab Injection (Subcutaneous Injection)TheSubmission of the listing application has been accepted. Insight database shows,ThisIt is the first subcutaneously injectable PD-1 antibody to be submitted for marketing approval in China.

In March this year, the US FDA has accepted the marketing application for subcutaneous injection of pembrolizumab.Used forKeytrudaAll previously approved solid tumor indications, PDUFA date is September 23, 2025.

Screenshot source: CDE official website

Subcutaneous Pembrolizumab（MK-3475A）Pembrolizumab with Berahyaluronidase alfa（ALT-B4）Composition: Berahyaluronidase alfa is a recombinant human hyaluronidase variant developed and produced by Alteogen, a company based in South Korea.

Hyaluronic acid is a major component of the extracellular matrix in skin and subcutaneous tissue, forming a high-viscosity "gel barrier" that restricts the diffusion of macromolecular drugs. Used in subcutaneous injection of antibody drugs.Hyaluronidase can degrade hyaluronic acid, reduce tissue viscosity, promote drug diffusion and absorption, and significantly increase the injection volume for subcutaneous administration.。

In November 2024, MSD announced the success of subcutaneous pembrolizumab in the pivotal Phase III study MK-3475A-D77, which aimed to compareSubcutaneous Injection of Pembrolizumab + ChemotherapyAndIntravenous injection of Keytruda + chemotherapy, used forAdult patients with metastatic non-small cell lung cancer(Regardless of PD-L1 TPS expression status)The effect of first-line treatment. In this study, subcutaneous pembrolizumabOnce every six weeks，The median injection time was 2 minutes., 4.8 milliliters each time.

2025 European Lung Cancer Conference (ELCC) Above, MSD announced the latest data from the MK-3475A-D77 study. The data shows:

• The study met its primary endpoint, showing the pharmacokinetics of subcutaneous pembrolizumab plus chemotherapy in the first-line treatment of adult patients with metastatic NSCLC. (PK) Not inferior to intravenous Keytruda + chemotherapy.

• In terms of secondary endpoints, the efficacy was consistent between the two groups. The ORR for the subcutaneous and intravenous groups were 45.4% vs 42.1%, the median DOR was 9.1 months vs 8.0 months, the median PFS was 8.1 months vs 7.8 months, and the median OS was not reached in either group.

• The two groups also demonstrated consistent safety, with the incidence of Grade ≥3 adverse events being 47% and 47.6% in the subcutaneous and intravenous groups, respectively.

Screenshot source:Insight Database

In addition, the results of a prospective observational time and motion descriptive analysis conducted concurrently with the 3475A-D77 study indicate that, compared to intravenous Keytruda,Subcutaneous injection of pembrolizumab reduced patients' chair-side stay time by 49.7%, respectively.(59.0 minutes vs 117.2 minutes)，The stay time in the treatment room was reduced by 47.4%.(Weekly average: 66.7 minutes vs 126.9 minutes), and enable medical staff in treatment preparation, medication administration, and patient monitoringTotal activity time decreased by 45.7%(Weekly average: 14.0 minutes vs 25.8 minutes)。

In addition to the 3475A-D77 trial, the subcutaneous pembrolizumab clinical development program also includes:

• Phase Ⅲ Trial 3475A-F84: Evaluation of Subcutaneous Pembrolizumab InjectionMonotherapyCompared with intravenous Keytruda monotherapy, used for treatmentHigh PD-L1 Expression in Metastatic NSCLCThe effect of first-line treatment on patients;

• Phase Ⅱ Trial 3475A-F65: Evaluating Subcutaneous Injection of PembrolizumabMonotherapy for Relapsed or Refractory Classical Hodgkin LymphomaAnd recurrent or refractoryPrimary Mediastinal Large B-Cell LymphomaThe effect.

• In addition, MSD is also conducting a Phase II study 3475A-F11 on patient preference to evaluate the preference of subcutaneous pembrolizumab injection compared with intravenous Keytruda as reported by subjects.

Notably, in April this year, Halozyme, the "enabler" of hyaluronidase technology, filed a lawsuit against MSD in the United States, accusing MSD's subcutaneous injection Keytruda of infringing on its patent. Industry insiders have analyzed that this lawsuit could impact the market launch process of Keytruda.

Insight database shows that globally, three subcutaneously injectable PD-1/L1 drugs have been approved for marketing, namely: Envafolimab developed by 3D Medicines/Alphamab Oncology/Simcere.（PD-L1）, Roche's Atezolizumab（PD-L1）、BMS's Nivolumab（PD-1）。

MSD's K drug is the world's second and China's first subcutaneous PD-1 submitted for marketing. In addition, Junshi's subcutaneous injection of toripalimab.（PD-1）, Pfizer's Subcutaneous Injection Sasanlimab（PD-1）Has entered Phase III.