Merck and Moderna have announced the commencement of INTerpath-009, a Phase 3 clinical trial assessing V940 (mRNA-4157) in combination with Keytruda (pembrolizumab) as an adjuvant treatment for non-small cell lung cancer (NSCLC). This trial focuses on patients with resectable Stage II, IIIA, or IIIB (N2) NSCLC who have not achieved a pathological complete response (pCR) following neoadjuvant treatment with Keytruda and platinum-based chemotherapy. The study aims to improve outcomes for patients with earlier stages of the disease. The first patients are now enrolling in Canada.
Trial Design and Objectives
INTerpath-009 is a global, randomized, double-blind Phase 3 trial designed to enroll 680 patients. Participants aged 18 and older with resected Stage II, IIIA, or IIIB (N2) NSCLC who did not achieve a pCR after neoadjuvant Keytruda plus platinum-based chemotherapy will be randomized 1:1 to receive either V940 (mRNA-4157) (1 mg every three weeks for up to nine doses) and Keytruda (400 mg every six weeks up to seven cycles) or placebo and Keytruda. The primary endpoint is disease-free survival (DFS), defined as the time from randomization to any recurrence, new primary NSCLC, or death due to any cause. Secondary endpoints include overall survival (OS), distant metastasis-free survival (DMFS), DFS2, lung cancer-specific survival (LCSS), safety, and quality of life.
Key eligibility criteria include a histologically confirmed diagnosis of Stage II, IIIA, or IIIB (N2) NSCLC, an ECOG performance status of 0 or 1, no pCR after neoadjuvant chemotherapy plus Keytruda, completed surgery, no evidence of disease by baseline imaging, and exclusion of EGFR mutations.
About mRNA-4157 (V940)
mRNA-4157 (V940) is an investigational individualized neoantigen therapy (INT) based on messenger RNA (mRNA). It consists of a synthetic mRNA coding for up to 34 neoantigens, designed and produced based on the unique mutational signature of the patient’s tumor DNA sequence. Upon administration, the algorithmically derived and RNA-encoded neoantigen sequences are translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity. This therapy is designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumor.
Lung Cancer Statistics and Current Treatment Landscape
Lung cancer remains the leading cause of cancer death worldwide. In 2022, there were approximately 2.4 million new cases and 1.8 million deaths globally. Non-small cell lung cancer accounts for about 80% of all lung cancer cases. The overall five-year survival rate for patients diagnosed with lung cancer in the United States is 25%. Improved survival rates are partly due to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, and 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.
Keytruda's Role
Keytruda (pembrolizumab) is an anti-PD-1 therapy that enhances the body’s immune system to detect and fight tumor cells. It is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes. Merck has an extensive immuno-oncology clinical research program with over 1,600 trials studying Keytruda across various cancers and treatment settings.
Previous Clinical Development Programs
Merck and Moderna have ongoing Phase 3 trials evaluating mRNA-4157 (V940) in combination with Keytruda as an adjuvant treatment in patients with resected high-risk melanoma and non-small cell lung cancer. They have also initiated Phase 2/3 trials evaluating mRNA-4157 (V940) in combination with Keytruda as neoadjuvant and adjuvant treatment in patients with resectable locally advanced cutaneous squamous cell carcinoma, renal cell carcinoma, and muscle-invasive urothelial carcinoma.
