Merck and Moderna have announced the commencement of the 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 first patients have been enrolled in Canada, marking the beginning of global recruitment.
Trial Design and Objectives
The INTerpath-009 trial is a global, randomized, double-blind study aiming to enroll 680 patients. Participants will be randomized 1:1 to receive either V940 (1 mg every three weeks for up to nine doses) plus Keytruda (400 mg every six weeks up to seven cycles) or placebo plus Keytruda. The primary endpoint is disease-free survival (DFS), measured from randomization to 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.
Key eligibility criteria include 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 EGFR mutations.
V940 (mRNA-4157): An Individualized Neoantigen Therapy
V940 (mRNA-4157) is an investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT). It consists of a synthetic mRNA coding for up to 34 neoantigens, designed based on the unique mutational signature of the patient’s tumor DNA. Upon administration, these RNA-encoded neoantigen sequences are translated, processed, and presented, stimulating an adaptive immune response.
Clinical Significance
Lung cancer remains the leading cause of cancer death worldwide, with non-small cell lung cancer accounting for approximately 80% of all cases. The overall five-year survival rate for lung cancer patients in the United States is 25%. This trial aims to improve outcomes for patients with earlier stages of NSCLC by leveraging individualized neoantigen therapy to train and activate an antitumor immune response.
Expert Commentary
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, stated, "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 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."
