Positive results from the pivotal Phase III MK-3475A-D77 trial for subcutaneous pembrolizumab in NSCLC

The trial is evaluating the noninferiority  from the pivotal Phase III MK-3475A-D77  Merck’s anti-PD-1 therapy, available for intravenous use as Keytruda, together with berahyaluronidase alfa, a hyaluronidase variant developed and manufactured by Alteogen Inc. (MK-3475A; “subcutaneous pembrolizumab”), administered with chemotherapy versus intravenous (IV) Keytruda administered with chemotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC).

The Phase III trial met its dual primary pharmacokinetic (PK) endpoints. Specifically, subcutaneous pembrolizumab administered every six weeks with chemotherapy demonstrated noninferiority of Area Under the Curve (AUC) exposure of pembrolizumab during the first dosing cycle, and trough concentration (Ctrough) of pembrolizumab measured at steady state, compared to IV Keytruda administered every six weeks in combination with chemotherapy. Additionally, secondary endpoints of efficacy and safety were generally consistent for subcutaneous pembrolizumab administered with chemotherapy compared with IV Keytruda administered with chemotherapy. These results, as well as those from ongoing analyses, will be presented at an upcoming medical meeting and shared with regulatory authorities worldwide.

“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,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “It is very encouraging to see positive Phase III results evaluating this fixed-dose combination of subcutaneous pembrolizumab, which was administered, on average, in approximately 2-3 minutes and has the potential to improve the patient experience as well as increase access for patients and healthcare providers compared to intravenous administration. We plan to discuss these results with regulatory authorities worldwide as soon as possible.”

In addition to the Phase III MK-3475A-D77 trial, Merck’s subcutaneous pembrolizumab clinical development program includes the Phase III MK-3475A-F84 trial evaluating subcutaneous pembrolizumab administered alone compared to IV Keytruda alone for the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), as well as the Phase II MK-3475A-F65 trial evaluating subcutaneous pembrolizumab administered alone in relapsed or refractory classical Hodgkin lymphoma and relapsed or refractory primary mediastinal large B-cell lymphoma. Merck is also conducting a Phase II patient preference study, MK-3475A-F11, evaluating participant-reported preference for subcutaneous pembrolizumab in comparison to IV Keytruda..

About MK-3475A-D77; MK-3475A-D77 is a randomized, open-label Phase III trial (ClinicalTrials.gov, NCT05722015 ) evaluating the subcutaneous administration of pembrolizumab together with berahyaluronidase alfa (also known as ALT-B4) administered every six weeks with chemotherapy compared to IV Keytruda administered every six weeks in combination with chemotherapy for the first-line treatment of adult patients with metastatic NSCLC. The study is designed to assess the dual primary PK endpoints of the AUC of pembrolizumab exposure during the first dosing cycle and the Ctrough of pembrolizumab measured at steady state. Secondary endpoints include additional PK parameters as well as efficacy (objective response rate, duration of response, progression-free survival and overall survival) and safety. The trial enrolled an estimated 378 patients who were randomized (2:1) to receive either subcutaneous pembrolizumab administered with chemotherapy or IV Keytruda in combination with chemotherapy.