Merck and Moderna have commenced a Phase 3 clinical trial, INTerpath-009, to assess the efficacy and safety of V940 (mRNA-4157), an individualized neoantigen therapy, in combination with KEYTRUDA (pembrolizumab) for patients with resected Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC). This trial specifically targets individuals who have not achieved a pathological complete response (pCR) following neoadjuvant treatment with KEYTRUDA and platinum-based chemotherapy.
The INTerpath-009 trial is a global, randomized, double-blind study involving 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), with secondary endpoints including overall survival (OS), distant metastasis-free survival (DMFS), and lung cancer-specific survival (LCSS).
Addressing Unmet Needs in NSCLC
Lung cancer remains the leading cause of cancer death worldwide. Non-small cell lung cancer accounts for approximately 80% of all lung cancer cases. While overall survival rates have improved, there is still a significant unmet need for more effective treatments, especially in earlier stages of the disease. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States.
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."
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 DNA sequence. Upon administration, these RNA-encoded neoantigen sequences are translated, processed, and presented, stimulating an adaptive immune response.
Trial Eligibility and Design
Key eligibility criteria include patients with histologically confirmed Stage II, IIIA, or IIIB (N2) NSCLC, an ECOG performance status of 0 or 1, and no pathological complete response (pCR) after neoadjuvant chemotherapy plus KEYTRUDA. Patients must have completed surgery with no evidence of disease by baseline imaging and must exclude epidermal growth factor receptor (EGFR) mutations.
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... 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."
KEYTRUDA's Role
KEYTRUDA (pembrolizumab) is an anti-programmed death receptor-1 (PD-1) therapy that enhances the immune system's ability 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, activating T lymphocytes against tumor cells.
Merck has an extensive immuno-oncology clinical research program with over 1,600 trials studying KEYTRUDA across various cancers and treatment settings. This program aims to understand KEYTRUDA's role in different cancers and identify factors predicting patient benefit, including exploring biomarkers.
Expanding the INTerpath Program
In addition to INTerpath-009, Merck and Moderna have initiated several other trials in 2024 to evaluate mRNA-4157 (V940) in combination with KEYTRUDA across different cancer types:
- Phase 2/3 trial in cutaneous squamous cell carcinoma (INTerpath-007, NCT06295809)
- Phase 2 trial in renal cell carcinoma (INTerpath-004, NCT06307431)
- Phase 2 trial in muscle-invasive urothelial carcinoma (INTerpath-005, NCT06305767)
