Merck and Moderna Launch Phase 3 Trial for mRNA-4157 Neoantigen Therapy Plus Pembrolizumab in NSCLC
INTerpath-009 investigates the treatment for patients with resectable stage 2, 3A or 3B non–small cell lung cancer.
Merck and Moderna launched the phase 3 INTerpath-009 clinical trial (NCT06623422) evaluating V940 (mRNA-4157) in combination with pembrolizumab (Keytruda; Merck) as adjuvant treatment for patients with resectable stage 2, 3A or 3B (N2) non–small cell lung cancer (NSCLC) who did not achieve a pathological complete response (pCR) after receiving neoadjuvant pembrolizumab plus platinum-based chemotherapy.1
Image Credit: © Dr_Microbe - stock.adobe.com
NSCLC accounts for approximately 85% of all cases, making it the most prevalent type of lung cancer. Standard treatment commonly includes combination of radiation therapy, chemotherapy, targeted therapy, and immunotherapy.2
“While the overall survival rates for patients with [NSCLC] have significantly improved in recent years, lung cancer continues to be the leading cause of cancer death worldwide,” Marjorie Green, MD, senior vice president and head of oncology in global clinical development at Merck Research Laboratories, said in a news release.3
Pembrolizumab has demonstrated significant success in treatment of NSCLC as a monotherapy and in combination with other agents. It is humanized monoclonal antibody that blocks the interaction between anti-programmed death receptor-1 (PD-1) and its ligands, PD- L1 and PD-L2, activating T lymphocytes which may affect both tumor cells and healthy cells.3
In the phase 3 INTerpath-009 trial, researchers are investigating neoadjuvant pembrolizumab in combination with adjuvant mRNA-4157 (V940; Merck, Moderna). MRNA-4157 is a novel investigational messenger RNA-based individualized neoantigen therapy (INT). It consists of synthetic coding for up to 34 neoantigens that are designed and produced based on the unique mutational signature of the patient’s tumor DNA. Upon administration, the neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation.3
INTerpath-009 is a global, randomized, double-blind phase 3 trial evaluating patients with resected (R0 or R1) stage 2, 3A, 3B (N2) NSCLC who did not achieve a pathologic complete response after neoadjuvant pembrolizumab plus platinum-based chemotherapy. The study includes 680 participants over the age of 18 who are randomized 1:1 to receive either V940 (mRNA-4157) (1 mg every 3 weeks for up to 9 doses) and pembrolizumab (400 mg every 6 weeks up to 7 cycles) or placebo (1 mg every 3 weeks for up to 9 doses) and pembrolizumab (400 mg every 6 weeks up to 7 cycles), after surgical resection.3
The primary end point of the trial is disease-free survival (DFS), defined as the time from randomization to any recurrence (local, locoregional, regional, or distant) or occurrence of new primary NSCLC. The secondary end points are overall survival, distant metastasis-free survival, DFS2, lung cancer-specific survival, safety, and quality of life.3
“We believe that our mRNA technology has the potential to improve the outcomes of those affected by lung cancer,” Kyle Holen, MD, senior vice president and head of development in therapeutics and oncology at Moderna, said in a news release. “Together, INTerpath-002 and INTerpath-009 are designed to demonstrate this potential in early-stage lung cancer, with and without prior neoadjuvant therapy.”3
REFERENCES
1. A study of pembrolizumab (mk-3475) with or without v940 in participants with non-small cell lung cancer (v940-009/interpath-009). ClinicalTrials.gov Identifier: NCT06623422. Updated October 2, 2024. Accessed October 31, 2024. https://clinicaltrials.gov/study/NCT06623422
2. Durvalumab receives fda approval for treatment of non-small cell lung cancer. Pharmacy Times. August 16, 2024. Accessed October 31, 2024. https://www.pharmacytimes.com/view/durvalumab-receives-fda-approval-for-treatment-of-non-small-cell-lung-cancer
3. Merck and moderna initiate phase 3 trial evaluating adjuvant v940 (mrna-4157) in combination with keytruda® (pembrolizumab) after neoadjuvant keytruda and chemotherapy in patients with certain types of non-small cell lung cancer (nsclc). Moderna. October 28, 2024. Accessed October 31, 2024. https://investors.modernatx.com/news/news-details/2024/Merck-and-Moderna-Initiate-Phase-3-Trial-Evaluating-Adjuvant-V940-mRNA-4157-in-Combination-with-KEYTRUDA-pembrolizumab-After-Neoadjuvant-KEYTRUDA-and-Chemotherapy-in-Patients-With-Certain-Types-of-Non-Small-Cell-Lung-Cancer-NSCLC/default.aspx
FDA Approves Rezafungin Injection for the Treatment of Candidemia, Invasive Candidiasis
March 27th 2023Rezafungin (Rezzayo; Cidara Therapeutics Inc, Melinta Therapeutics LLC) is the first new treatment option approved for individuals with candidemia and invasive candidiasis in more than a decade.
