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.
