Merck and Moderna have commenced the Phase III INTerpath-009 trial to investigate V940 (mRNA-4157), an individualized neoantigen therapy (INT), in conjunction with Keytruda (pembrolizumab) as an adjuvant treatment for patients with resectable non-small cell lung cancer (NSCLC). The trial targets patients who have undergone neoadjuvant treatment with Keytruda and chemotherapy but did not achieve a pathological complete response (pCR). The first patients have been recruited in Canada, marking the beginning of global recruitment efforts.
The INTerpath-009 trial is a global, randomized, double-blind study enrolling 680 patients aged 18 years and older. Participants will be randomized in a 1:1 ratio after surgical resection to receive either 1 mg of V940 every three weeks for up to nine doses combined with 400 mg of Keytruda every six weeks for up to seven cycles, or placebo plus Keytruda. The primary endpoint is disease-free survival, defined as the time from randomization to recurrence, new primary NSCLC, or death. Secondary endpoints include overall survival, distant metastasis-free survival (DMFS), lung cancer-specific survival, safety, and quality of life.
Marjorie Green, SVP, head of oncology, global clinical development, Merck Research Laboratories, stated, "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."
This Phase III trial builds on earlier positive results from the Phase IIb KEYNOTE-942/mRNA-4157-P201 trial, which assessed V940 in combination with Keytruda in patients with high-risk melanoma post-resection. The combination demonstrated sustained benefits in recurrence-free survival and DMFS. Furthermore, a Phase II/III trial has been initiated to evaluate the combination as neoadjuvant and adjuvant treatment in patients with resectable locally advanced Stage II-IV cutaneous squamous cell carcinoma. Additional Phase II trials are underway to assess the combination in renal cell carcinoma and muscle-invasive urothelial carcinoma.
Kyle Holen, MD, SVP, head of development, therapeutics and oncology, Moderna, commented, "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."
NSCLC accounts for approximately 85% of all lung cancers. The American Cancer Society estimates that in 2024, there will be about 234,580 new cases of lung cancer and 125,070 deaths in the United States. The median age at diagnosis is 70 years, with most patients diagnosed over 65.
