Merck, recognized as MSD outside the United States and Canada, has announced encouraging topline outcomes from the pivotal phase 3 MK-3475A-D77 study. This investigation is analyzing whether the subcutaneous delivery of pembrolizumab—a renowned anti-PD-1 therapy by Merck, commercially known as Keytruda when administered intravenously—combined with berahyaluronidase alfa, an advanced hyaluronidase form created by Alteogen Inc. (MK-3475A; “subcutaneous pembrolizumab”), closely parallels the intravenous Keytruda when both are used with chemotherapy as a first-line treatment for adults with metastatic non-small cell lung cancer (NSCLC).
In the phase 3 study, primary pharmacokinetic (PK) objectives were successfully met. Specifically, subcutaneous pembrolizumab delivered bi-weekly along with chemotherapy showed it was not inferior in terms of Pembrolizumab’s Area Under the Curve (AUC) exposure during the initial dosage cycle, as well as the trough concentration (Ctrough) at a steady state, compared to the intravenous Keytruda given every six weeks with chemotherapy. Furthermore, the effectiveness and safety secondary endpoints were mostly consistent between the subcutaneous pembrolizumab coupled with chemotherapy and the IV Keytruda with chemotherapy. These outcomes, alongside data from ongoing evaluations, will be presented at an upcoming medical conference and submitted to global regulatory personnel.
“Keytruda has significantly altered the approach to treating severe cancer types, yet our pursuit of further innovations to benefit patients continues,” expressed Dr. Marjorie Green, who serves as Merck Research Laboratories’ Senior Vice President and Head of Oncology, Global Clinical Development. “The positive phase 3 outcomes concerning subcutaneous pembrolizumab’s fixed-dose formula, administered in roughly 2-3 minutes on average, is promising. This could enhance the treatment experience and extend accessibility for both patients and medical practitioners when compared to intravenous methods. Our goal is to engage with worldwide regulatory bodies about these findings expeditiously.”
Beyond the MK-3475A-D77 phase 3 research, Merck’s clinical program for subcutaneous pembrolizumab includes the phase 3 MK-3475A-F84 investigation, assessing subcutaneous pembrolizumab alone against IV Keytruda alone for first-line treatment of patients with metastatic NSCLC exhibiting high PD-L1 expression (tumor proportion score [TPS] =50%). Additionally, the phase 2 MK-3475A-F65 trial examines the solo administration of subcutaneous pembrolizumab for cases of relapsed or refractory classical Hodgkin lymphoma and relapsed or refractory primary mediastinal large B-cell lymphoma. A phase 2 study (MK-3475A-F11) also evaluates patient-reported preferences between subcutaneous pembrolizumab and IV Keytruda.
The MK-3475A-D77 study is a randomized, open-label phase 3 effort (ClinicalTrials.gov, NCT05722015) reviewing the subcutaneous delivery of pembrolizumab with berahyaluronidase alfa (known as ALT-B4) every six weeks alongside chemotherapy, versus the intravenous Keytruda with chemotherapy as a first-line treatment for adults with metastatic NSCLC. The trial aims to evaluate the primary PK indicators such as Pembrolizumab’s AUC exposure during the initial dosage cycle and the steady-state Ctrough. Secondary aspects include more PK parameters, efficacy (objective response rate, response duration, progression-free survival, overall survival), and safety. Approximately 378 patients were enrolled and randomly assigned (2:1) to receive either subcutaneous pembrolizumab with chemotherapy or IV Keytruda paired with chemotherapy.
Keytruda functions as an anti-programmed death receptor-1 (PD-1) therapy that enhances the immune system’s capacity to detect and combat tumor cells. It is a humanized monoclonal antibody hindering interactions between PD-1 and its ligands, PD-L1 and PD-L2, therefore activating T lymphocytes that can impact tumor and healthy cells.
Merck leads the immuno-oncology clinical research landscape with the largest program, encompassing over 1,600 studies on Keytruda across numerous cancer types and treatment frameworks. The Keytruda research initiative aims to comprehend Keytruda’s role in various cancers and identify factors that might predict patient response to the treatment, including examining diverse biomarkers.