• 13 Dec 2023
• Admin
• News Article

Merck, Moderna begin INTerpath-002 phase 3 study of V940 in combo with Keytruda for adjuvant treatment of patients with certain types of resected NSCLC

Merck, known as MSD outside of the United States and Canada, and Moderna, Inc. announced the initiation of INTerpath-002, a pivotal phase 3 randomized clinical trial evaluating V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with Keytruda, Merck’s anti-PD-1 therapy, as adjuvant treatment in patients with completely resected (R0) Stage II, IIIA or IIIB (with nodal involvement [N2]) non-small cell lung cancer (NSCLC). Global recruitment of the INTerpath-002 has begun, and the first patients enrolled in Australia.

“As lung cancer is the leading cause of cancer death worldwide, there is a need for continued scientific advancements to help fight this disease at earlier stages when patients have the best chance for better outcomes,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “By combining Keytruda with V940 (mRNA-4157), a promising new modality, we are researching innovative new approaches for earlier stage non-small cell lung cancer.”

“Addressing lung cancer reflects the constant struggle between medical innovation and biological complexity. Each patient's cancer presents a labyrinth of genetic mutations, driving a novel approach of individualized medicines manufactured based on the distinct molecular tumour profile for each patient,” said Kyle Holen, M.D., Moderna's senior vice president and head of development, therapeutics and oncology. “We believe an individualized neoantigen therapy can be this catalyst for innovation and drive us forward towards the next frontier of cancer care. I’m incredibly thankful for the patients, investigators, and clinical trial sites for helping us in this mission.”

As previously announced, in addition to INTerpath-002, the combination of V940 (mRNA-4157) plus Keytruda is being investigated in INTerpath-001, formerly referred to as V940-001 (NCT05933577), a global, randomized, double-blind, placebo- and active-comparator-controlled Phase 3 trial evaluating approximately 1,089 patients with resected high-risk (Stage IIB-IV) melanoma. INTerpath-001 is actively screening in 14 countries (Australia, Belgium, Canada, Chile, France, Germany, Greece, Israel, Italy, Poland, Portugal, Spain, Turkey and the United Kingdom), representing 38 sites. The companies plan to continue expansion of the comprehensive clinical development program for V940 (mRNA-4157) to additional tumour types.

V940 (mRNA-4157) 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.

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 V940 (mRNA-4157) with Keytruda may provide a meaningful benefit over Keytruda alone.

INTerpath-002 is a global, randomized, double-blind, placebo- and active-comparator-controlled phase 3 trial evaluating approximately 868 patients with completely resected Stage II, IIIA or IIIB [N2] NSCLC. Following complete surgical resection and adjuvant chemotherapy, participants 18 years and older will be randomized 1:1 to receive V940 (mRNA-4157) (1 mg every three weeks for up to nine doses) and Keytruda (400 mg every six weeks for up to nine cycles) versus Keytruda alone for approximately one year or until disease recurrence or any of the other criteria for discontinuation of study intervention are met. The primary endpoint is disease-free survival (DFS), defined as the time from randomization to any recurrence or occurrence of new primary NSCLC as assessed by the investigator, or death due to any cause. The secondary endpoints are overall survival (OS), distant metastasis-free survival (DMFS), lung cancer specific survival (LCSS), safety, and quality of life.

Key eligibility criteria for the trial include: completion of surgical resection of histologically confirmed Stage II, IIIA or IIIB (N2) squamous or nonsquamous NSCLC, confirmation that epidermal growth factor receptor (EGFR)-directed therapy is not indicated as primary therapy, no evidence of disease at the time of providing documented consent for the main study, prior treatment with at least one dose of adjuvant therapy with standard-of-care platinum-based doublet chemotherapy up to four cycles, and no more than 24 weeks between surgical resection with curative intent and the first dose of Keytruda.

Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 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 in the US, accounting for about 81% of all cases. In the US, the overall five-year survival rate for patients diagnosed with lung cancer is 26.2%, which is a 22% improvement over the last five years. 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. Only 4.5% of people in the US who are eligible were screened for lung cancer in 2022.

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.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying Keytruda across a wide variety of cancers and treatment settings. The Keytruda clinical program 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.