• 05 Apr 2024
• Admin
• News Article

Merck Begins Phase 3 Trial of MK-1084 & Keytruda Combo

Merck starts phase 3 trial of MK-1084 in combo with Keytruda for first-line treatment of certain patients with metastatic NSCLC

Overview

Merck, known as MSD outside of the United States and Canada, announced it has initiated a phase 3 clinical trial evaluating MK-1084, an investigational oral selective KRAS G12C inhibitor, in combination with Keytruda for the first-line treatment of certain patients with metastatic non-small cell lung cancer (NSCLC) whose tumours harbour KRAS G12C mutations and express PD-L1 (tumour proportion score [TPS] =50%).

Words from Merck Research Laboratories

• “KRAS is among the most prevalent mutations in cancer and KRAS G12C is the most common KRAS mutation in patients with non-small cell lung cancer,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. 
• “Based on early evidence showing MK-1084 in combination with Keytruda had a manageable safety profile and promising anti-tumour activity, we are now proceeding to a larger phase 3 trial to evaluate this combination in certain patients with metastatic non-small cell lung cancer.”

NCT06345729 Trial

• Merck has initiated a phase 3, randomized, double-blind, multicenter clinical trial (NCT06345729) evaluating once daily MK-1084 in combination with Keytruda administered once every three weeks compared with Keytruda plus placebo in previously untreated patients with KRAS G12C-mutated metastatic NSCLC with a PD-L1 TPS =50%.
• The trial will enroll approximately 600 patients globally. 
• The primary endpoints of the study are progression-free survival and overall survival, and key secondary endpoints include objective response rate and duration of response.

MK-1084 Investigation Under Trial

• MK-1084 is currently being evaluated in a phase 1, open-label multicenter clinical trial (NCT05067283) to assess safety, tolerability, pharmacokinetics and efficacy of MK-1084 as monotherapy and as part of various combination therapies in patients with KRAS G12C mutant advanced solid tumors. 
• Preliminary safety and efficacy data from this trial were previously presented at the European Society for Medical Oncology (ESMO) Congress in 2023.

Collaboration for Development of MK-1084

MK-1084 is being developed through a collaboration with Taiho Pharmaceutical Co. Ltd and Astex Pharmaceuticals (UK), a wholly owned subsidiary of Otsuka Pharmaceutical Co., Ltd. This collaboration was announced in January 2020.

About MK-1084

• MK-1084 is an investigational, potent and specific KRAS G12C covalent inhibitor. 
• Mutations in KRAS are among the most prevalent mutations found in cancer, occurring with high frequency in non-small cell lung cancer, pancreatic, urogenital and colorectal cancers. 
• The KRAS G12C mutation is the most frequently observed KRAS mutation in patients, occurring in approximately 14% of non-small cell lung cancers (adenocarcinoma). 
• Despite decades of research and recognition of the therapeutic importance of targeting KRAS, the development of small molecule inhibitors targeting KRAS mutations has been challenging.

About Lung Cancer

• Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. 
• Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. 
• In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. 
• Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. 
• Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.

Merck Work on Lung Cancer

• Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. 
• Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. 
• In NSCLC, Keytruda has six approved US indications and is approved for advanced disease in more than 95 countries. 
• Among Merck’s research efforts are trials focused on evaluating Keytruda in earlier stages of lung cancer as well as identifying new combinations and co-formulations with Keytruda.

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 Program

• Merck has the industry’s largest immuno-oncology clinical research program. 
• 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.