Merck and Moderna have commenced a pivotal Phase 3 clinical trial, named INTerpath-009, to assess the efficacy of mRNA-4157 (V940) in combination with Keytruda (pembrolizumab) as an adjuvant treatment for patients with resectable Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC). This trial focuses on patients who have not achieved a pathological complete response (pCR) following neoadjuvant treatment with Keytruda and platinum-based chemotherapy. The global recruitment for INTerpath-009 has begun, with the first patients now enrolling in Canada.
Dr. Marjorie Green, Senior Vice President and Head of Oncology, Global Clinical Development, Merck Research Laboratories, stated, "While the overall survival rates for patients with non-small cell lung cancer have significantly improved in recent years, lung cancer continues to be the leading cause of cancer death worldwide." She added, "We are pleased to expand the INTerpath clinical trial programme with Moderna, evaluating V940 (mRNA-4157), a promising new modality, in combination with Keytruda to pursue meaningful advances for lung cancer and bring more options to patients with earlier stages of disease, where we potentially can have the most impact."
Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology, commented, "We are excited to build on our ongoing collaboration with our colleagues at Merck by expanding our research efforts for patients with NSCLC." He further noted, "We believe that our mRNA technology has the potential to improve the outcomes of those affected by lung cancer and together, INTerpath-002 and INTerpath-009 are designed to demonstrate this potential in early-stage lung cancer, with and without prior neoadjuvant therapy."
Trial Design and Endpoints
INTerpath-009 is a global, randomized, double-blind Phase 3 trial involving 680 patients with resected Stage II, IIIA, or IIIB (N2) NSCLC who did not achieve a pCR after neoadjuvant Keytruda plus platinum-based chemotherapy. Participants aged 18 years and older 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. 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/cytologically confirmed diagnosis of Stage II, IIIA, or IIIB (N2) NSCLC, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, no pCR by local testing after neoadjuvant chemotherapy plus Keytruda, completed surgery, no disease by baseline imaging, and exclusion of epidermal growth factor receptor (EGFR) mutation.
About mRNA-4157 (V940)
mRNA-4157 (V940) is an investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT). 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. Upon administration, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity. Individualized neoantigen therapies are designed to train and activate an anti-tumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumor.
Lung Cancer Burden
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 is 25% in the United States. Improved survival rates are attributed 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 Mechanism of Action
Keytruda is an anti-programmed death receptor-1 (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, affecting both tumor cells and healthy cells.
