Merck and Moderna Start Phase 3 Trial of V940 with KEYTRUDA in Certain NSCLC Patients

Merck and Moderna have announced the launch of INTerpath-009, a critical Phase 3 clinical trial, aimed at evaluating the effectiveness of the investigational neoantigen therapy V940 (mRNA-4157) in combination with KEYTRUDA (pembrolizumab) for patients with resectable Stage II, IIIA, or IIIB non-small cell lung cancer (NSCLC). This trial is specifically for those who did not achieve a pathological complete response (pCR) after pre-surgery treatment involving KEYTRUDA and platinum-based chemotherapy. The global recruitment for this trial has commenced, with the first patients already being enrolled in Canada.

Dr. Marjorie Green, a senior vice president at Merck, noted the significant improvements in survival rates for NSCLC patients over recent years, though lung cancer remains the leading cause of cancer death worldwide. She expressed enthusiasm about expanding the INTerpath clinical trial program with Moderna, highlighting the potential for V940 (mRNA-4157) to offer meaningful advancements in treating early-stage lung cancer.

Dr. Kyle Holen of Moderna echoed this sentiment, underscoring the potential of mRNA technology to improve outcomes for lung cancer patients. The collaborative effort between Merck and Moderna, exemplified by the INTerpath-002 and INTerpath-009 trials, aims to demonstrate the efficacy of V940 (mRNA-4157) in early-stage lung cancer, both with and without prior neoadjuvant therapy.

The INTerpath-009 trial is designed to evaluate 680 patients with resected Stage II, IIIA, or IIIB (N2) NSCLC, who have not achieved pCR after initial therapy. The trial's primary endpoint is disease-free survival (DFS), while secondary endpoints include overall survival (OS), distant metastasis-free survival (DMFS), lung cancer-specific survival (LCSS), safety, and quality of life. Patients will receive either V940 (mRNA-4157) and KEYTRUDA or a placebo and KEYTRUDA in a randomized, double-blind setup.

Merck and Moderna have a robust ongoing clinical development program featuring several Phase 3 trials. These include trials for resected high-risk melanoma (INTerpath-001), and NSCLC (INTerpath-002), as well as a two-part Phase 2/3 trial for cutaneous squamous cell carcinoma (INTerpath-007), a Phase 2 trial for renal cell carcinoma (INTerpath-004), and another Phase 2 trial for muscle-invasive urothelial carcinoma (INTerpath-005).

The investigational therapy V940 (mRNA-4157) is a novel mRNA-based individualized neoantigen therapy. It consists of synthetic mRNA coding for up to 34 neoantigens, designed based on the unique mutational signature of a patient’s tumor. This personalization aims to train and activate the patient’s immune system to generate specific T-cell responses against the tumor. When combined with KEYTRUDA, an immunotherapy that enhances the body's ability to detect and fight tumor cells, V940 has shown promise in previous trials for melanoma, indicating a potential benefit over using KEYTRUDA alone.

Lung cancer remains the deadliest form of cancer worldwide, with non-small cell lung cancer being the most common subtype. In 2022, there were approximately 2.4 million new cases and 1.8 million deaths globally due to lung cancer. Despite improvements in survival rates owing to early detection and new therapies, there is still a significant unmet need for early detection and effective treatments, as a large percentage of lung cancer cases are diagnosed at advanced stages.

KEYTRUDA (pembrolizumab) is an anti-PD-1 therapy that enhances the immune system's ability to fight tumor cells. It is approved for various cancer treatments, including NSCLC, melanoma, and several others. Merck's extensive clinical research program for KEYTRUDA involves over 1,600 trials across different cancers and treatment settings, aiming to understand and predict patient responses to the therapy.

In summary, the launch of the INTerpath-009 trial represents a significant step in the ongoing collaboration between Merck and Moderna, aiming to provide new, effective treatment options for patients with early-stage lung cancer using cutting-edge mRNA technology and immunotherapy.