Merck and Moderna have initiated the Phase 3 INTerpath-009 clinical trial to assess V940 (mRNA-4157) in combination with pembrolizumab (Keytruda) for patients with resectable stage II, IIIA, or IIIB non-small cell lung cancer (NSCLC). This study targets patients who have undergone neoadjuvant pembrolizumab with platinum-based chemotherapy but did not achieve a pathological complete response.
Lung cancer remains the leading cause of cancer death worldwide, accounting for approximately 2.4 million new cases and 1.8 million deaths in 2022. The overall 5-year survival rate for lung cancer patients in the US is only 25%. NSCLC represents about 80% of all lung cancer cases.
Study Design and Treatment
The INTerpath-009 trial (NCT06077760) will enroll 680 participants with Stage II, IIIA, or IIIB (N2) NSCLC. Following surgical resection, patients will be randomized to receive either 1 mg of V940 every 3 weeks for 9 doses combined with 400 mg of pembrolizumab every 6 weeks for up to 7 cycles, or placebo with pembrolizumab. V940 is a synthetic mRNA coding for up to 34 neoantigens, designed to train and activate an antitumor immune response. Pembrolizumab, an anti-PD-1 therapy, enhances the immune system's ability to detect and fight tumor cells by blocking the interaction of PD-1 with PD-L1 and PD-L2.
Endpoints and Objectives
The primary endpoint of the INTerpath-009 trial is disease-free survival, measured from the time of randomized treatment to any local recurrence or new primary NSCLC. Secondary endpoints include overall survival, distant metastasis-free survival, lung cancer-specific survival, safety, and quality of life.
Expert Commentary
Marjorie Green, MD, senior vice president and head of oncology and global clinical development at 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."
Kyle Holen, MD, senior vice president and head of development of therapeutics and oncology at Moderna, 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."
