2-3 Minutes for Administration! Keytruda Subcutaneous Injection Phase III Study Success

On November 19, Merck announced that the pivotal Phase III MK-3475A-D77 study achieved positive results. The study evaluated the pharmacokinetics (PK), efficacy, and safety of the subcutaneous injection of pembrolizumab (MK-3475A) compared to the intravenous injection of pembrolizumab (Keytruda) when combined with chemotherapy as first-line treatment for adult patients with metastatic non-small cell lung cancer (NSCLC).

MK-3475A-D77 is a randomized, open-label Phase III clinical trial (NCT05722015) that included 378 patients. The dual primary endpoints of the study were: the area under the drug concentration-time curve (AUC) of pembrolizumab during the first treatment cycle, and the lowest plasma concentration (Ctrough) of pembrolizumab at steady-state. Secondary endpoints included other PK parameters, efficacy measures (including objective response rate, duration of response, progression-free survival, and overall survival), and safety endpoints. 

The results indicated that the study met its dual primary endpoints. Specifically, the subcutaneous injection of MK-3475A combined with chemotherapy showed non-inferiority in terms of AUC exposure during the first treatment cycle compared to the intravenous Keytruda combination, and the Ctrough at steady-state also showed non-inferiority. Additionally, secondary efficacy and safety endpoints were generally consistent between the two groups.

Merck plans to present detailed results at upcoming medical meetings and submit the relevant data to regulatory agencies. 

Dr. Marjorie Green, Senior Vice President and Head of Global Clinical Development for Oncology at Merck Research Laboratories, stated, "Keytruda has already transformed the treatment of some of the deadliest cancers, but we are continuously exploring other innovative therapies that may benefit patients. The positive results of the Phase III study of subcutaneous pembrolizumab combination therapy are very encouraging. On average, the administration time for MK-3475A is approximately 2-3 minutes, which could improve patient experience and accessibility for both patients and healthcare providers compared to intravenous infusion. We plan to discuss these results with regulatory authorities worldwide as soon as possible."

In addition to the Phase III MK-3475A-D77 study, Merck's clinical development program for the subcutaneous injection of pembrolizumab also includes the Phase III MK-3475A-F84 study and the Phase II MK-3475A-F65 study. The Phase III MK-3475A-F84 study aims to evaluate the efficacy and safety of subcutaneous MK-3475A compared to intravenous Keytruda in first-line treatment for patients with high PD-L1 expression (TPS≥50%) with metastatic NSCLC. The Phase II MK-3475A-F65 study aims to assess the efficacy and safety of subcutaneous pembrolizumab compared to the intravenous formulation for the treatment of relapsed or refractory classical Hodgkin lymphoma and relapsed or refractory primary mediastinal large B-cell lymphoma. Additionally, Merck is conducting a Phase II patient preference study (MK-3475A-F11) to assess patients' preferences for subcutaneous versus intravenous pembrolizumab. 

On September 13 of this year, Roche’s atezolizumab subcutaneous injection was approved by the FDA for all intravenous indications for which atezolizumab is approved in the U.S. for adults, becoming the first FDA-approved PD-(L)1 inhibitor for subcutaneous administration.