Merck, known as MSD outside of the United States and Canada, and Moderna have announced the initiation of INTerpath-009, a Phase 3 clinical trial evaluating V940 (mRNA-4157) in combination with Keytruda (pembrolizumab) as an adjuvant treatment for non-small cell lung cancer (NSCLC). The trial targets patients with resectable Stage II, IIIA, or IIIB (N2) NSCLC who did not achieve a pathological complete response (pCR) after receiving neoadjuvant Keytruda plus platinum-based chemotherapy.
Trial Design and Objectives
INTerpath-009 is a global, randomized, double-blind study designed to enroll 680 patients. Participants will be randomized 1:1 to receive either V940 (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), lung cancer-specific survival (LCSS), safety, and quality of life.
Patient Eligibility
Key eligibility criteria include patients with histologically confirmed Stage II, IIIA, or IIIB (N2) NSCLC, an ECOG performance status of 0 or 1, no pCR after neoadjuvant chemotherapy plus Keytruda, completed surgery, and exclusion of epidermal growth factor receptor (EGFR) mutations.
V940 (mRNA-4157): An Individualized Neoantigen Therapy
V940 is an investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT) consisting of a synthetic mRNA coding for up to 34 neoantigens. It is 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.
Clinical Significance
"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," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "We are pleased to expand the INTerpath clinical trial program 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."
Broader Clinical Program
Merck and Moderna are also evaluating mRNA-4157 (V940) in combination with Keytruda as an adjuvant treatment in patients with resected high-risk melanoma (INTerpath-001) and non-small cell lung cancer (INTerpath-002). Additional trials are ongoing for cutaneous squamous cell carcinoma (INTerpath-007), renal cell carcinoma (INTerpath-004), and urothelial carcinoma (INTerpath-005).
Lung Cancer Statistics
Lung cancer is the leading cause of cancer death worldwide, with approximately 2.4 million new cases and 1.8 million deaths globally in 2022. Non-small cell lung cancer accounts for about 80% of all cases. The overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.
