Merck and Moderna Launch Phase 3 Trial of mRNA Neoantigen Therapy V940 with Keytruda in Resected Non-Small Cell Lung Cancer

▎Edited by the WuXi AppTec content team

Recently, MSD and Moderna announced the launch of the pivotal phase 3 clinical trial INTerpath-002,To evaluate the individualized neoantigen therapy V940 (mRNA-4157) in combination with Keytruda as adjuvant treatment for patients with completely resected (R0) stage II, IIIA, or IIIB non-small cell lung cancer (NSCLC).The global recruitment for INTerpath-002 has begun, with the first group of patients already enrolled in Australia.

INTerpath-002 is a global, randomized, double-blind, placebo-controlled, and active-controlled Phase 3 clinical trial evaluating approximately 868 patients with completely resected Stage II, IIIA, or IIIB NSCLC. Following complete surgical resection and adjuvant chemotherapy, subjects aged 18 years and older will be randomized 1:1 to receive either V940 (1 mg every three weeks for up to 9 doses) in combination with Keytruda (400 mg every six weeks for up to 9 cycles), or Keytruda alone, for a treatment duration of approximately one year, until disease recurrence or meeting other criteria for discontinuation of study intervention.The primary endpoint of the trial is disease-free survival (DFS), defined as the time from randomization to investigator-assessed recurrence, occurrence of a new primary NSCLC, or death from any cause.The secondary endpoints were overall survival (OS), distant metastasis-free survival (DMFS), lung cancer-specific survival (LCSS), safety, and quality of life.。

The main enrollment criteria for this trial include: completion of surgical resection for histologically confirmed stage II, IIIA, or IIIB squamous or non-squamous NSCLC; confirmation that epidermal growth factor receptor (EGFR)-targeted therapy is not suitable as the primary treatment; no evidence of disease at the time of providing consent for the main study; prior receipt of at least one dose of standard adjuvant chemotherapy with platinum doublet, up to four cycles; and an interval of no more than 24 weeks between curative surgery and the first use of Keytruda.

In addition to INTerpath-002, the combination therapy of V940 and Keytruda is also being studied in another clinical trial, INTerpath-001 (formerly known as V940-001, NCT05933577), a global, randomized, double-blind, placebo-controlled, and active-controlled Phase 3 clinical trial evaluating approximately 1,089 high-risk (Stage IIB-IV) melanoma patients who have undergone surgical resection. INTerpath-001 is being conducted across 38 clinical trial sites in 14 countries. The company plans to continue expanding the clinical development program for V940 into other types of tumors.

V940 is a novel personalized neoantigen therapy based on mRNA developed by Moderna.Composed of artificially synthesized mRNA molecules encoding up to 34 neoantigens, this synthetic mRNA is designed and produced based on the unique mutational signature of the patient's tumor DNA sequence.When administering medication to patients, the neoantigen sequences encoded by RNA are endogenously translated and undergo cellular antigen processing and presentation—a crucial step in adaptive immunity.Personalized neoantigen therapy aims to elicit specific T-cell responses based on the unique mutational signature of a patient's tumor, thereby training and activating an anti-tumor immune response.Keytruda isUnder MSDA humanized monoclonal antibody against programmed death receptor-1 (PD-1) that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2. It helps detect and combat tumor cells by enhancing the ability of the human immune system.

[1] Merck and Moderna Initiate INTerpath-002, a Phase 3 Study Evaluating V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab) for Adjuvant Treatment of Patients with Certain Types of Resected Non-Small Cell Lung Cancer，Retrieved December 12, 2023 from https://www.businesswire.com/news/home/20231211889403/en

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