Merck's Phase 3 Trial of Subcutaneous Pembrolizumab Meets Primary Endpoints

RAHWAY, N.J.--Merck (NYSE: MRK), known as MSD outside the United States and Canada, has revealed promising results from the pivotal Phase 3 MK-3475A-D77 trial. This study assesses the noninferiority of subcutaneous administration of pembrolizumab, Merck’s anti-PD-1 therapy (commercially known as KEYTRUDA® for intravenous use), along with berahyaluronidase alfa, a hyaluronidase variant from Alteogen Inc. (referred to as “subcutaneous pembrolizumab”). This combination, administered with chemotherapy, is compared to intravenous (IV) KEYTRUDA combined with chemotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC).

The Phase 3 trial achieved its dual primary pharmacokinetic (PK) endpoints. Specifically, subcutaneous pembrolizumab administered every six weeks with chemotherapy showed noninferiority in the Area Under the Curve (AUC) exposure of pembrolizumab during the initial dosing cycle, and the trough concentration (Ctrough) of pembrolizumab measured at steady state. These results were comparable to those of IV KEYTRUDA administered every six weeks with chemotherapy. Secondary endpoints, such as efficacy and safety, were generally consistent between the subcutaneous pembrolizumab and IV KEYTRUDA, when both were administered with chemotherapy. Further results and ongoing analyses are scheduled to be presented at an upcoming medical conference and shared with global regulatory authorities.

Dr. Marjorie Green, Merck Research Laboratories' senior vice president and head of oncology, global clinical development, expressed optimism about the Phase 3 results, stating, “KEYTRUDA has revolutionized cancer treatment, and we are committed to pursuing innovations that benefit patients.” She highlighted the potential of the fixed-dose combination of subcutaneous pembrolizumab, typically administered in roughly 2-3 minutes, to enhance the patient experience and accessibility compared to intravenous administration. Discussions with regulatory authorities are forthcoming.

In addition to the MK-3475A-D77 trial, Merck's subcutaneous pembrolizumab development program includes the Phase 3 MK-3475A-F84 trial. This study evaluates subcutaneous pembrolizumab alone versus IV KEYTRUDA alone for first-line treatment of patients with metastatic NSCLC exhibiting high PD-L1 expression (tumor proportion score [TPS] ≥50%). There is also the Phase 2 MK-3475A-F65 trial, which explores subcutaneous pembrolizumab alone in relapsed or refractory classical Hodgkin lymphoma and relapsed or refractory primary mediastinal large B-cell lymphoma. Moreover, Merck is conducting a Phase 2 patient preference study, MK-3475A-F11, to assess participant-reported preferences for subcutaneous pembrolizumab compared to IV KEYTRUDA.

The MK-3475A-D77 trial is a randomized, open-label Phase 3 study (ClinicalTrials.gov, NCT05722015). It compares the subcutaneous administration of pembrolizumab combined with berahyaluronidase alfa (ALT-B4) every six weeks with chemotherapy, against IV KEYTRUDA with chemotherapy for the first-line treatment of adult patients with metastatic NSCLC. The study aims to evaluate dual primary PK endpoints: the AUC of pembrolizumab during the first dosing cycle and the Ctrough of pembrolizumab at steady state. Secondary endpoints include additional PK parameters, efficacy measures (objective response rate, duration of response, progression-free survival, and overall survival), and safety. Approximately 378 patients were enrolled and randomized (2:1) to receive either the subcutaneous pembrolizumab with chemotherapy or IV KEYTRUDA with chemotherapy.

KEYTRUDA® (pembrolizumab) injection, 100 mg, is an anti-PD-1 therapy designed to enhance the immune system’s capability to detect and combat tumor cells. As a humanized monoclonal antibody, KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thus activating T lymphocytes. This activation affects both tumor and healthy cells. Merck leads the field in immuno-oncology clinical research, with more than 1,600 trials investigating KEYTRUDA across various cancers and treatment settings. The clinical program aims to grasp the role of KEYTRUDA across different cancers and identify biomarkers that might predict a patient's likelihood of benefiting from treatment with KEYTRUDA.

In the U.S., KEYTRUDA is approved for multiple indications, including in combination with chemotherapy for metastatic nonsquamous NSCLC and as monotherapy for patients with high PD-L1 expressing NSCLC. This extensive research and approval underscore Merck’s commitment to advancing cancer treatment and improving patient outcomes through innovative therapy combinations and administration methods.