MSD (Merck & Co in the US and Canada) and Moderna have commenced a phase 3 clinical trial, named INTerpath-009, to assess the efficacy of their personalized cancer vaccine, V940 (mRNA-4157), in conjunction with MSD's anti-PD-1 therapy, Keytruda (pembrolizumab), for patients with stage 2 to 3b non-small cell lung cancer (NSCLC). This study focuses on patients who have undergone surgery and neoadjuvant chemotherapy but have not achieved a pathological complete response (pCR), placing them at high risk of recurrence.
The INTerpath-009 trial is designed as an international, multi-center study that will enroll approximately 680 patients. These patients will receive neoadjuvant chemotherapy combined with Keytruda, followed by surgery, and then adjuvant therapy with both Keytruda and V940. The primary endpoint of the trial is disease-free survival (DFS), while secondary endpoints include overall survival (OS). The first patients have already been recruited in Canada.
Addressing Unmet Needs in NSCLC Treatment
Despite advancements in NSCLC treatment, a significant proportion of patients with stage 2 to 3b disease experience recurrence following surgery, necessitating additional lines of therapy. While surgery aims for curative outcomes, recurrence rates range from one-third to one-half of patients. Keytruda has been approved for surgery-spanning immunotherapy in this patient population since October 2023. This new trial aims to determine whether adding V940 to the treatment regimen can further decrease the risk of relapse.
V940: A Personalized Approach to Cancer Immunotherapy
V940 (mRNA-4157) is a personalized vaccine designed to target up to 34 cancer neoantigens derived from individual patients' tumors. This approach allows for a tailored immune response against the specific mutations present in each patient's cancer. The ongoing trials, including INTerpath-002 (adjuvant therapy post-surgery without neoadjuvant treatment) and INTerpath-001 (adjuvant treatment for resected high-risk stage 2b to 4 melanoma), underscore the potential of V940 across various cancer types.
Expert Perspectives
Dr. Marjorie Green, head of oncology, global clinical development, at Merck Research Laboratories, emphasized the importance of this research, stating that while overall survival rates for NSCLC have improved, lung cancer remains the leading cause of cancer death worldwide. She described V940 as a "promising new modality" that, alongside Keytruda, could deliver "meaningful advances for lung cancer and bring more options to patients with earlier stages of disease, where we potentially can have the most impact."
MSD partnered with Moderna on V940 in October 2022, marking the first program activated under a 2016 alliance focused on developing individualized cancer vaccines for a range of cancers.
