Merck (MSD) announced positive topline results from the Phase 3 MK-3475A-D77 trial, evaluating subcutaneous pembrolizumab in combination with berahyaluronidase alfa for the first-line treatment of metastatic non-small cell lung cancer (NSCLC). The trial compared this subcutaneous formulation to intravenous KEYTRUDA, both administered with chemotherapy.
The MK-3475A-D77 trial met its dual primary pharmacokinetic (PK) endpoints, demonstrating noninferiority of subcutaneous pembrolizumab compared to IV KEYTRUDA. Specifically, the area under the curve (AUC) exposure of pembrolizumab during the first dosing cycle and the trough concentration (Ctrough) of pembrolizumab at steady state were noninferior to IV KEYTRUDA when both were administered every six weeks with chemotherapy.
Secondary endpoints, including efficacy and safety, were generally consistent between the subcutaneous pembrolizumab and IV KEYTRUDA arms. Full results will be presented at an upcoming medical meeting and shared with regulatory authorities worldwide.
Implications of Subcutaneous Administration
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, noted the potential benefits of subcutaneous pembrolizumab. The subcutaneous formulation can be administered in approximately 2-3 minutes, potentially improving the patient experience and increasing access for both patients and healthcare providers compared to intravenous administration.
Ongoing Clinical Development Program
Merck's subcutaneous pembrolizumab clinical development program includes several ongoing trials:
- MK-3475A-F84: A 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: A Phase 2 trial assessing subcutaneous pembrolizumab alone in relapsed or refractory classical Hodgkin lymphoma and relapsed or refractory primary mediastinal large B-cell lymphoma.
- MK-3475A-F11: A Phase 2 patient preference study comparing subcutaneous pembrolizumab to IV KEYTRUDA.
Trial Design of MK-3475A-D77
The MK-3475A-D77 trial (NCT05722015) is a randomized, open-label Phase 3 trial evaluating subcutaneous pembrolizumab with berahyaluronidase alfa administered every six weeks with chemotherapy compared to IV KEYTRUDA administered every six weeks in combination with chemotherapy for the first-line treatment of adult patients with metastatic NSCLC. The trial enrolled an estimated 378 patients who were randomized (2:1) to receive either subcutaneous pembrolizumab administered with chemotherapy or IV KEYTRUDA in combination with chemotherapy. The primary endpoints were the AUC of pembrolizumab exposure during the first dosing cycle and the Ctrough of pembrolizumab measured at steady state. Secondary endpoints included additional PK parameters as well as efficacy (objective response rate, duration of response, progression-free survival and overall survival) and safety.
