Merck and Moderna have announced the initiation of INTerpath-009, a Phase 3 clinical trial evaluating V940 (mRNA-4157) in combination with KEYTRUDA (pembrolizumab) as adjuvant treatment for patients with resectable Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC). The trial focuses on patients who did not achieve a pathological complete response (pCR) after receiving neoadjuvant KEYTRUDA plus platinum-based chemotherapy. Enrollment has begun in Canada, with global recruitment underway.
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. 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."
Kyle Holen, M.D., Moderna's senior vice president and head of development, Therapeutics and Oncology, added, "We are excited to build on our ongoing collaboration with our colleagues at Merck by expanding our research efforts for patients with NSCLC. 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 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 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, and exclusion of EGFR mutations.
About V940 (mRNA-4157)
mRNA-4157 (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 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 antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumor.
Lung Cancer Context
Lung cancer remains the leading cause of cancer death worldwide, with approximately 2.4 million new cases and 1.8 million deaths in 2022. 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 2024 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.
