Subcutaneous Pembrolizumab Non-Inferior to IV Keytruda in NSCLC Phase III Trial
核心洞察
MSD's Phase III MK-3475A-D77 trial demonstrated non-inferiority of subcutaneous pembrolizumab plus chemotherapy versus intravenous Keytruda plus chemotherapy in first-line metastatic NSCLC (搜索).
The trial met its dual primary pharmacokinetic endpoints, showing comparable exposure and trough concentration of pembrolizumab between subcutaneous and IV formulations.
Secondary endpoints related to efficacy and safety were observed to be steady between the subcutaneous and IV forms of pembrolizumab, when administered alongside chemotherapy.
MSD (Merck & Co., Inc.) has announced positive topline results from the Phase III MK-3475A-D77 trial, which evaluated the non-inferiority of subcutaneous pembrolizumab in combination with chemotherapy compared to intravenous (IV) Keytruda (pembrolizumab) plus chemotherapy for the first-line treatment of metastatic non-small cell lung cancer (搜索) (NSCLC (搜索)). The study's findings suggest that the subcutaneous formulation could offer a more convenient administration route without compromising efficacy or safety.
The open-label trial randomized approximately 378 patients in a 2:1 ratio to receive either subcutaneous pembrolizumab with chemotherapy or IV Keytruda with chemotherapy, administered every six weeks. The study met its dual primary pharmacokinetic endpoints, demonstrating that subcutaneous pembrolizumab, co-administered with Alteogen’s berahyaluronidase alfa, achieved non-inferior area under the curve (AUC) exposure and trough concentration (Ctrough) of pembrolizumab at steady state compared to IV Keytruda.
Efficacy and Safety
Secondary endpoints related to efficacy and safety were observed to be steady between the subcutaneous and IV forms of pembrolizumab, when administered alongside chemotherapy. This suggests that the subcutaneous formulation maintains the therapeutic benefits of IV Keytruda while potentially offering a more convenient administration route.
Clinical Significance
Dr. Marjorie Green, head of oncology, global clinical development, and senior vice-president at MSD Research Laboratories, highlighted the potential benefits of the subcutaneous formulation. "Keytruda has helped transform the way we treat some of the deadliest forms of cancer, yet we continue to pursue additional innovations that may benefit patients," she stated. She also noted that the subcutaneous pembrolizumab was administered, on average, in approximately two to three minutes, potentially improving patient experience and increasing access for patients and healthcare providers compared to intravenous administration.
Broader Clinical Program
The MK-3475A-D77 trial is part of a broader clinical development program for pembrolizumab. This includes the Phase III MK-3475A-F84 study comparing subcutaneous pembrolizumab alone to IV Keytruda alone in metastatic NSCLC (搜索) patients with high PD-L1 (搜索) expression. Additionally, the Phase II MK-3475A-F65 trial is evaluating the subcutaneous form in relapsed or refractory classical Hodgkin lymphoma (搜索) and primary mediastinal large B-cell lymphoma. MSD is also conducting the Phase II MK-3475A-F11 patient preference trial to evaluate patient-reported preference for subcutaneous pembrolizumab compared to its IV counterpart.
MSD plans to discuss these results with regulatory authorities worldwide as soon as possible, potentially paving the way for a new, more convenient administration option for pembrolizumab in NSCLC (搜索) and other indications.