Merck and Moderna Initiate Phase 3 Study for Adjuvant Treatment of Non-Small Cell Lung Cancer

Merck (NYSE: MRK) and Moderna, Inc. (Nasdaq: MRNA) have announced the initiation of INTerpath-002, a pivotal Phase 3 randomized clinical trial. This trial evaluates V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, as adjuvant treatment in patients with completely resected (R0) Stage II, IIIA or IIIB (with nodal involvement [N2]) non-small cell lung cancer (NSCLC). Global recruitment for the INTerpath-002 trial has begun, with the first patients enrolled in Australia.

Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, emphasized the need for continued scientific advancements to combat lung cancer, the leading cause of cancer death worldwide. The combination of KEYTRUDA with V940 (mRNA-4157) represents an innovative approach to treating earlier-stage NSCLC.

Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology, highlighted the complexity of lung cancer and the potential of individualized neoantigen therapies to drive forward the next frontier of cancer care. These 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.

V940 (mRNA-4157) is a novel investigational messenger RNA (mRNA)-based individualized neoantigen therapy consisting of synthetic mRNA coding for up to 34 neoantigens. It is designed and produced based on the unique mutational signature of the DNA sequence of the patient’s tumor. Upon administration, the RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.

The INTerpath-002 trial is a global, randomized, double-blind, placebo- and active-comparator-controlled Phase 3 trial evaluating approximately 868 patients with completely resected Stage II, IIIA or IIIB [N2] NSCLC. Following complete surgical resection and adjuvant chemotherapy, participants 18 years and older will be randomized to receive V940 (mRNA-4157) and KEYTRUDA versus KEYTRUDA alone for approximately one year or until disease recurrence or any of the other criteria for discontinuation of study intervention are met. The primary endpoint is disease-free survival (DFS), with secondary endpoints including overall survival (OS), distant metastasis-free survival (DMFS), lung cancer specific survival (LCSS), safety, and quality of life.

Lung cancer remains the leading cause of cancer death worldwide, with non-small cell lung cancer accounting for about 81% of all lung cancer cases in the U.S. The overall five-year survival rate for patients diagnosed with lung cancer is 26.2%, a 22% improvement over the last five years, attributed to earlier detection, reduction in smoking, advances in diagnostic and surgical procedures, and the introduction of new therapies. However, early detection and screening remain critical, as 44% of lung cancer cases are not found until they are advanced.