Merck's subcutaneous formulation of Keytruda (pembrolizumab) plus berahyaluronidase alfa, in combination with chemotherapy, has met its primary pharmacokinetic (PK) endpoints in the Phase 3 MK-3475A-D77 trial for patients with previously untreated metastatic non-small cell lung cancer (NSCLC). The trial compared the subcutaneous formulation to the intravenous (IV) formulation of Keytruda, both administered with chemotherapy.
The randomized, open-label study evaluated the noninferiority of subcutaneous Keytruda plus chemotherapy versus IV Keytruda plus chemotherapy in the first-line treatment of metastatic NSCLC. The primary endpoints were the area under the curve exposure of Keytruda during the first dosing cycle and the trough concentration (Ctrough) of Keytruda at steady state.
The results demonstrated that subcutaneous Keytruda, administered every six weeks, achieved noninferiority in both primary PK endpoints compared to IV Keytruda, also given every six weeks. The average administration time for the subcutaneous formulation was approximately two to three minutes.
Secondary endpoints, including efficacy (objective response rate, duration of response, progression-free survival, and overall survival) and safety, were generally consistent between the two treatment arms. Full results will be presented at an upcoming medical meeting and shared with regulatory authorities worldwide.
Potential Benefits of Subcutaneous Administration
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, at Merck Research Laboratories, highlighted the potential benefits of the subcutaneous formulation. She noted that it could improve the patient experience and increase access for patients and healthcare providers due to the shorter administration time compared to intravenous administration.
Trial Design and Patient Population
The MK-3475A-D77 trial enrolled approximately 378 patients with histologically or cytologically confirmed squamous or nonsquamous NSCLC. Eligible patients were 18 years or older with a life expectancy of at least three months. Patients were excluded if they had received prior systemic therapies for their disease within four weeks of randomization, or radiotherapy within two weeks of the study's start.
Patients were randomized in a 2:1 ratio to receive either subcutaneous Keytruda plus berahyaluronidase alfa with chemotherapy every six weeks or IV Keytruda with chemotherapy every six weeks. In addition to the primary PK endpoints, the trial also assessed various secondary PK parameters, efficacy endpoints, and safety.
Mechanism of Action of Keytruda
Keytruda is an anti-PD-1 therapy that enhances the immune system's ability to detect and fight tumor cells. The IV formulation of Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which can affect both tumor cells and healthy cells.
