Merck's pembrolizumab, marketed as Keytruda, continues to show promise across a spectrum of cancers, with recent data highlighting its efficacy in non-small cell lung cancer (NSCLC) and ongoing investigations into its potential in rarer malignancies. A Phase III trial (MK-3475A-D77) recently reported positive topline outcomes, evaluating a subcutaneous formulation of pembrolizumab in combination with chemotherapy for first-line treatment of metastatic NSCLC.
Subcutaneous Pembrolizumab Achieves Non-Inferiority in NSCLC
The MK-3475A-D77 study was an open-label trial involving approximately 378 participants, randomized in a 2:1 ratio. Participants received either subcutaneous pembrolizumab with chemotherapy or intravenous (IV) Keytruda with chemotherapy, administered every six weeks. The trial's findings indicated that subcutaneous pembrolizumab, when co-administered with Alteogen’s berahyaluronidase alfa, achieved non-inferiority in terms of area under the curve (AUC) exposure and trough concentration (Ctrough) at steady state, compared to IV Keytruda. The study successfully met its dual primary pharmacokinetic endpoints.
Secondary endpoints, focusing on efficacy and safety, were consistent between the subcutaneous and IV formulations of pembrolizumab when administered alongside chemotherapy. This new formulation, administered on average in approximately two to three minutes, holds the potential to improve patient experience and increase access for both patients and healthcare providers, according to Dr. Marjorie Green, head of oncology global clinical development and senior vice president at MSD Research Laboratories.
Expanding Applications of Pembrolizumab
Beyond NSCLC, pembrolizumab is being explored for a variety of other cancers. It is currently under development for conditions such as Kaposi sarcoma and myxoid liposarcoma, reflecting its broad potential as an antineoplastic immunomodulating agent. Pembrolizumab's existing indications cover a wide range of cancers, including melanoma, Hodgkin lymphoma, urothelial carcinoma, and cervical cancer, among others.
Ongoing Clinical Trials
Several clinical trials are underway to further investigate pembrolizumab's capabilities. The Phase III MK-3475A-F84 study is comparing subcutaneous pembrolizumab alone to IV Keytruda alone in metastatic NSCLC patients with high PD-L1 expression. Additionally, the Phase II MK-3475A-F65 trial is assessing the subcutaneous form in relapsed or refractory classical Hodgkin lymphoma 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.
Future Directions
MSD plans to discuss the Phase III results of the subcutaneous pembrolizumab study with regulatory authorities worldwide. This development, along with ongoing research into new formulations and applications, underscores the commitment to expanding the therapeutic potential of pembrolizumab and improving outcomes for patients across diverse cancer types.
