Merck Announces Positive Topline Data from Pivotal Phase 3 Study of Subcutaneous Pembrolizumab in First-Line Metastatic NSCLC

Rahway, New Jersey, USA,2025Year3Month27Day——MSD (the corporate name of Merck & Co., Inc., located in Rahway, New Jersey, U.S.) announced the first set of data from the pivotal Phase III 3475A-D77 study, which evaluated the efficacy and safety of a subcutaneous formulation of pembrolizumab combined with berahyaluronidase alfa (MK-3475A, hereinafter referred to as "subcutaneous pembrolizumab"). Berahyaluronidase alfa is a recombinant human hyaluronidase variant developed and manufactured by Alteogen. The study results were presented at the 2025 European Lung Cancer Conference (ELCC 2025, abstract number #8MO) and simultaneously published in the Annals of Oncology.

3475A-D77 Study is a randomized, open-label Phase III trial (ClinicalTrials.gov, NCT05722015) designed to evaluate subcutaneous pembrolizumab administered every six weeks in combination with chemotherapy compared to intravenous pembrolizumab administered every six weeks.[1]Combination chemotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC): Efficacy and safety regardless of PD-L1 TPS expression levels. The dual primary pharmacokinetic (PK) endpoints of the study are the area under the concentration-time curve (AUC) for pembrolizumab exposure during the first dosing cycle and the minimum concentration (Ctrough) of pembrolizumab measured at steady state. Secondary endpoints include other PK parameters, as well as efficacy metrics (ORR, DOR, PFS, and OS) and safety. The study enrolled a total of 377 patients, who were randomly assigned (2:1) to receive either subcutaneous pembrolizumab in combination with chemotherapy or intravenous pembrolizumab in combination with chemotherapy.

An observational time-motion descriptive analysis study was conducted concurrently in the 3475A-D77 study. This global research included 17 study centers across 8 countries from the 3475A-D77 trial. The primary endpoints were: patient chair time during treatment, total time spent in the treatment room, and the total procedural time for healthcare professionals involved in tasks related to the preparation, administration of subcutaneous pembrolizumab, and patient monitoring. Time data were measured by trained observers using a stopwatch, excluding durations related to chemotherapy administration. Descriptive statistics were calculated using weighted means (WM) to adjust for imbalanced sample sizes across countries, and statistical differences between the subcutaneous and intravenous groups were analyzed using a linear mixed model. These results were presented in a poster at ELCC (Poster Number #33P).

Dr. Enriqueta Felip, head of the Thoracic Tumor Group at the Vall d'Hebron Institute of Oncology in Spain, stated, "As a clinician, the data on the subcutaneous injection of pembrolizumab is exciting to me. This method of administration has the potential to save precious treatment time for patients."

Dr. Marjorie Green, Senior Vice President of Merck & Co., Inc. Laboratories and Head of Oncology and Global Clinical Development, stated: "Pembrolizumab has already helped transform the treatment landscape for some cancers. Building on this breakthrough therapy, we continue to innovate to optimize the treatment experience for patients and healthcare providers. The subcutaneous injection formulation is expected to become a clinically valuable new option – not only potentially improving drug accessibility but also helping save medical time. We look forward to collaborating with regulatory agencies worldwide to bring more innovative treatment options to healthcare providers and patients as soon as possible."

Apart from the 3475A-D77 trial, MSD's subcutaneous pembrolizumab clinical development program also includes the Phase III 3475A-F84 trial, evaluating monotherapy subcutaneous injection versus intravenous injection for first-line treatment of metastatic NSCLC with high PD-L1 expression (TPS≥50%); the Phase II 3475A-F65 trial, assessing monotherapy for relapsed/refractory classical Hodgkin lymphoma and primary mediastinal large B-cell lymphoma; and the Phase II 3475A-F11 patient preference study, comparing patient acceptance of subcutaneous versus intravenous injection.

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[1]Instructions for Pembrolizumab Injection: Pembrolizumab must be administered via intravenous infusion over a period of more than 30 minutes. Pembrolizumab must not be administered via intravenous push or rapid intravenous injection.