Merck and Moderna have commenced the Phase 3 INTerpath-009 clinical trial (NCT06623422) to evaluate mRNA-4157 (V940) in combination with pembrolizumab (Keytruda; Merck) as adjuvant treatment for patients with resectable stage 2, 3A, or 3B (N2) non-small cell lung cancer (NSCLC) who did not achieve a pathological complete response (pCR) after receiving neoadjuvant pembrolizumab plus platinum-based chemotherapy.
NSCLC represents approximately 85% of all lung cancer cases, making it the most prevalent type. Standard treatment approaches commonly involve a combination of radiation therapy, chemotherapy, targeted therapy, and immunotherapy.
"While the overall survival rates for patients with [NSCLC] have significantly improved in recent years, lung cancer continues to be the leading cause of cancer death worldwide," said Marjorie Green, MD, senior vice president and head of oncology in global clinical development at Merck Research Laboratories.
Pembrolizumab, a humanized monoclonal antibody, has demonstrated success in treating NSCLC both as a monotherapy and in combination with other agents. It functions by blocking the interaction between programmed death receptor-1 (PD-1) and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which can affect both tumor cells and healthy cells.
The INTerpath-009 trial is investigating neoadjuvant pembrolizumab in combination with adjuvant mRNA-4157 (V940; Merck, Moderna). MRNA-4157 is a novel investigational messenger RNA-based individualized neoantigen therapy (INT). It consists of synthetic coding for up to 34 neoantigens designed and produced based on the unique mutational signature of the patient’s tumor DNA. Upon administration, the neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation.
INTerpath-009 is a global, randomized, double-blind Phase 3 trial evaluating patients with resected (R0 or R1) stage 2, 3A, 3B (N2) NSCLC who did not achieve a pathologic complete response after neoadjuvant pembrolizumab plus platinum-based chemotherapy. The study includes 680 participants over the age of 18 who are randomized 1:1 to receive either V940 (mRNA-4157) (1 mg every 3 weeks for up to 9 doses) and pembrolizumab (400 mg every 6 weeks up to 7 cycles) or placebo (1 mg every 3 weeks for up to 9 doses) and pembrolizumab (400 mg every 6 weeks up to 7 cycles), after surgical resection.
The primary endpoint of the trial is disease-free survival (DFS), defined as the time from randomization to any recurrence (local, locoregional, regional, or distant) or occurrence of new primary NSCLC. The secondary endpoints are overall survival, distant metastasis-free survival, DFS2, lung cancer-specific survival, safety, and quality of life.
"We believe that our mRNA technology has the potential to improve the outcomes of those affected by lung cancer," said Kyle Holen, MD, senior vice president and head of development in therapeutics and oncology at Moderna. "Together, INTerpath-002 and INTerpath-009 are designed to demonstrate this potential in early-stage lung cancer, with and without prior neoadjuvant therapy."
