Merck, Moderna Begin Phase 3 Trial of mRNA-4157 In Combo With Keytruda For NSCLC

Merck, Moderna begin phase 3 trial of mRNA-4157 in combo with Keytruda after neoadjuvant Keytruda & chemotherapy in patients with certain types of NSCLC

Overview

Merck, known as MSD outside of the United States and Canada, and Moderna, Inc. announced the initiation of INTerpath-009, a pivotal phase 3 randomized clinical trial evaluating V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, as adjuvant treatment for patients with resectable Stage II, IIIA or IIIB (N2) non-small cell lung cancer (NSCLC) who did not achieve a pathological complete response (pCR) after receiving neoadjuvant Keytruda plus platinum-based chemotherapy. Global recruitment in INTerpath-009 has begun, and the first patients have now started enrolling in Canada.

From Merck Research Laboratories

• 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,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. 
• We are pleased to expand the INTerpath clinical trial programme 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.

From the Moderna's Senior Vice President: Oncology

• We are excited to build on our ongoing collaboration with our colleagues at Merck by expanding our research efforts for patients with NSCLC,” said Kyle Holen, M.D., Moderna's senior vice president and head of development, therapeutics and oncology. 
• 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.

Initiation of Phase 3

Merck and Moderna have initiated phase 3 randomized clinical trials evaluating mRNA-4157 (V940) in combination with Keytruda as an adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma (INTerpath-001, NCT05933577 ) and non-small cell lung cancer (INTerpath-002, NCT06077760 ).

Phase 2/3 in 2024 by The Duo

• In 2024, Merck and Moderna also initiated a two-part phase 2/3 randomized clinical trial evaluating mRNA-4157 (V940) in combination with Keytruda as neoadjuvant and adjuvant treatment in patients with resectable locally advanced Stage II-IV (M0) cutaneous squamous cell carcinoma (INTerpath-007, NCT06295809 ).
• It is a phase 2 randomized clinical trial evaluating mRNA-4157 (V940) in combination with Keytruda as adjuvant treatment in patients with intermediate-high-risk, high-risk, or M1 no evidence of disease renal cell carcinoma (INTerpath-004, NCT06307431 ), and a phase 2 randomized clinical trial evaluating mRNA-4157 (V940) in combination with Keytruda as adjuvant treatment in patients with high-risk muscle-invasive urothelial carcinoma post-radical resection (INTerpath-005, NCT06305767 ).

The new mRNA-4157

• mRNA-4157 (V940) is a novel investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT) consisting of a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient’s tumour. 
• Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.

The Individualized Neoantigen Therapies

• Individualized neoantigen therapies are designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumour. 
• Keytruda is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumour cells. 
• As previously announced from the phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating patients with high-risk stage III/IV melanoma, combining mRNA-4157 (V940) with Keytruda may provide a meaningful benefit over Keytruda alone. 
• Merck and Moderna continue to evaluate and expand the V940 INTerpath clinical development program for additional tumour types and treatment settings.

INTerpath-009 Trial

• INTerpath-009 is a global, randomized, double-blind phase 3 trial evaluating 680 patients with resected (R0 or R1) Stage II, IIIA, IIIB (N2) NSCLC who did not achieve a pCR after neoadjuvant Keytruda plus platinum-based chemotherapy. 
• Following surgical resection, participants 18 years and older will be randomized 1:1 to receive either V940 (mRNA-4157) (1 mg every three weeks for up to nine doses) and Keytruda (400 mg every six weeks up to seven cycles) or placebo (1 mg every three weeks for up to nine doses) and Keytruda (400 mg every six weeks up to seven cycles). 
• The primary endpoint is disease-free survival (DFS), defined as the time from randomization to any recurrence (local, locoregional, regional, or distant), occurrence of new primary NSCLC, as assessed by the investigator, or death due to any cause, whichever occurs first. 
• The secondary endpoints are overall survival (OS), distant metastasis-free survival (DMFS), DFS2, lung cancer-specific survival (LCSS), safety, and quality of life.

Key Eligibility Criteria for the Trial Include: 

• patients who have histologically/cytologically confirmed diagnosis of Stage II, IIIA, or IIIB (N2) NSCLC (American Joint Committee on Cancer [AJCC] 8th Edition),
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, no pCR by local testing after neoadjuvant chemotherapy plus Keytruda, completed surgery, with no disease by baseline imaging, and exclude epidermal growth factor receptor (EGFR) mutation.

About Lung Cancer

• Lung cancer is the leading cause of cancer death worldwide. 
• In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. 
• Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. 
• In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States.
• Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. 
• Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.

About Keytruda

• Keytruda is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumour cells. 
• Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumour cells and healthy cells.

Immuno-Oncology Clinical Research Programme by Merck

• Merck has the industry’s largest immuno-oncology clinical research programme. 
• There are currently more than 1,600 trials studying Keytruda across a wide variety of cancers and treatment settings. 
• The Keytruda clinical programme seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.

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