Merck’s Phase 3 Trial of Subcutaneous Pembrolizumab+ Berahyaluronidaseshows Positive Response

Merck’s Phase 3 Trial of Subcutaneous Pembrolizumab+ Berahyaluronidaseshows Positive Response

By, Admin 21 November 2024

Merck’s phase 3 trial of subcutaneous pembrolizumab with berahyaluronidase alfa meets primary endpoints

Overview

Merck, known as MSD outside of the United States and Canada, announced positive topline results from the pivotal phase 3 MK-3475A-D77 trial. The trial is evaluating the noninferiority of subcutaneous administration of pembrolizumab, 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 Positive Endpoints

  • The phase 3 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.

From Global Clinical Development: Merck Research Laboratories

  • 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 3 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.

Other Studies on Pembrolizumab

  • In addition to the phase 3 MK-3475A-D77 trial, Merck’s subcutaneous pembrolizumab clinical development programme includes the phase 3 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 tumours have high PD-L1 expression (tumour proportion score [TPS] =50%), as well as the phase 2 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 2 patient preference study, MK-3475A-F11, evaluating participant-reported preference for subcutaneous pembrolizumab in comparison to IV Keytruda.

About MK-3475A-D77 trials 

  • MK-3475A-D77 is a randomized, open-label phase 3 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.

About the Therapy: Keytruda

  • Keytruda is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumour cells. 
  • 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 may affect both tumour cells and healthy cells.

Immuno-Oncology Clinical Research Programme by Merck

  • Merck has the industry’s largest immuno-oncology clinical research programme. 
  • There are currently more than 1,600 trials studying Keytruda across a wide variety of cancers and treatment settings. 
  • The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.

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