Merck's subcutaneous formulation of pembrolizumab, co-administered with berahyaluronidase alfa, has achieved positive topline results in the pivotal Phase 3 MK-3475A-D77 trial. This new formulation aims to provide a non-inferior alternative to the intravenous (IV) administration of pembrolizumab (KEYTRUDA®) in combination with chemotherapy for first-line treatment of metastatic non-small cell lung cancer (NSCLC).
The Phase 3 trial met its dual primary pharmacokinetic (PK) endpoints. The subcutaneous pembrolizumab, administered every six weeks with chemotherapy, demonstrated non-inferiority in both Area Under the Curve (AUC) exposure during the first dosing cycle and trough concentration (Ctrough) at steady state, when compared to IV KEYTRUDA administered every six weeks with chemotherapy.
Efficacy and Safety
Secondary endpoints evaluating efficacy and safety were generally consistent between the subcutaneous and IV pembrolizumab arms. Full results from the trial will be presented at an upcoming medical meeting and shared with regulatory authorities worldwide.
Potential Benefits of Subcutaneous Administration
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, noted the potential benefits of the subcutaneous formulation. "It is very encouraging to see positive Phase 3 results evaluating this fixed-dose combination of subcutaneous pembrolizumab, which was administered, on average, in approximately 2-3 minutes and has the potential to improve the patient experience as well as increase access for patients and healthcare providers compared to intravenous administration."
Trial Design and Patient Population
The MK-3475A-D77 trial is a randomized, open-label Phase 3 study (NCT05722015) comparing subcutaneous pembrolizumab with berahyaluronidase alfa to IV KEYTRUDA, both in combination with chemotherapy, for first-line treatment of metastatic NSCLC. The trial randomized approximately 378 patients in a 2:1 ratio to receive either subcutaneous pembrolizumab with chemotherapy or IV KEYTRUDA with chemotherapy. The primary endpoints focused on pharmacokinetic parameters, while secondary endpoints included objective response rate, duration of response, progression-free survival, overall survival, and safety.
Ongoing Clinical Development Program
Merck's subcutaneous pembrolizumab clinical development program includes several other ongoing trials:
- MK-3475A-F84: Phase 3 trial evaluating subcutaneous pembrolizumab alone versus IV KEYTRUDA alone for first-line treatment of metastatic NSCLC with high PD-L1 expression (TPS ≥50%).
- MK-3475A-F65: Phase 2 trial evaluating subcutaneous pembrolizumab alone in relapsed or refractory classical Hodgkin lymphoma and relapsed or refractory primary mediastinal large B-cell lymphoma.
- MK-3475A-F11: Phase 2 patient preference study evaluating participant-reported preference for subcutaneous pembrolizumab compared to IV KEYTRUDA.
