Subcutaneous Pembrolizumab Meets Primary Endpoints in Phase 3 NSCLC Trial
Key Insights
Merck's subcutaneous pembrolizumab, co-administered with berahyaluronidase alfa, met its dual primary pharmacokinetic endpoints in a Phase 3 trial for metastatic NSCLC.
The trial compared subcutaneous pembrolizumab plus chemotherapy to intravenous KEYTRUDA plus chemotherapy as a first-line treatment.
Secondary endpoints of efficacy and safety were generally consistent between the subcutaneous and intravenous pembrolizumab groups.
MerckView company profile has announced positive topline results from the Phase 3 MK-3475A-D77 trial, evaluating a subcutaneous formulation of pembrolizumabSearch drug, the company's anti-PD-1Search term therapy, for the first-line treatment of metastatic non-small cell lung cancerSearch disease (NSCLCSearch disease). The trial assessed the noninferiority of subcutaneous pembrolizumab, co-administered with berahyaluronidase alfa, versus intravenous (IV) KEYTRUDASearch drug, both in combination with chemotherapy.
Key Findings from the MK-3475A-D77 Trial
The Phase 3 trial met its dual primary pharmacokinetic (PK) endpoints. Subcutaneous pembrolizumabSearch drug, administered every six weeks with chemotherapy, demonstrated noninferiority in Area Under the Curve (AUC) exposure during the first dosing cycle and trough concentration (Ctrough) at steady state, compared to IV KEYTRUDASearch drug administered every six weeks with chemotherapy. Secondary endpoints of efficacy and safety were generally consistent between the two administration routes.
Implications for Patient Care
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, MerckView company profile 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 pembrolizumabSearch drug, 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 (ClinicalTrials.gov, NCT05722015View clinical trial ) comparing subcutaneous pembrolizumabSearch drug with berahyaluronidase alfa to IV KEYTRUDASearch drug, both administered every six weeks with chemotherapy, for the first-line treatment of adult patients with metastatic NSCLCSearch disease. The trial enrolled an estimated 378 patients, randomized 2:1 to receive either subcutaneous pembrolizumab 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 at steady state. Secondary endpoints included additional PK parameters, efficacy (objective response rate, duration of response, progression-free survival, and overall survival), and safety.
Further Development of Subcutaneous Pembrolizumab
MerckView company profile's subcutaneous pembrolizumabSearch drug clinical development program includes the Phase 3 MK-3475A-F84 trial, evaluating subcutaneous pembrolizumab alone versus IV KEYTRUDASearch drug alone for first-line treatment of metastatic NSCLCSearch disease with high PD-L1Search term expression (TPS ≥50%). Additionally, the Phase 2 MK-3475A-F65 trial is assessing subcutaneous pembrolizumab alone in relapsed or refractory classical Hodgkin lymphomaSearch disease and relapsed or refractory primary mediastinal large B-cell lymphoma. Merck is also conducting a Phase 2 patient preference study, MK-3475A-F11, comparing patient-reported preference for subcutaneous pembrolizumab versus IV KEYTRUDA.
About Pembrolizumab
KEYTRUDASearch drug (pembrolizumabSearch drug) is an anti-programmed death receptor-1 (PD-1Search term) therapy that enhances the immune system's ability to detect and fight tumor cells. It is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1Search term and PD-L2, activating T lymphocytes to target tumor cells.