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The initiation of the second clinical trial in the INTerpath program represents rapid expansion in research for additional tumor types for individualized neoantigen therapy, V940 (mRNA-4157)
RAHWAY, N.J. & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Moderna, Inc. (Nasdaq: MRNA), today 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.
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“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 tumor 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 tumor types.
About V940 (mRNA-4157)
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 tumor. 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 tumor. KEYTRUDA is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumor 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.
About INTerpath-002 (NCT06077760)
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.
For further information, please see: https://clinicaltrials.gov/study/NCT06077760?term=NCT06077760&rank=1.
About lung cancer
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 U.S., accounting for about 81% of all cases. In the U.S., 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 U.S. who are eligible were screened for lung cancer in 2022.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
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 tumor 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 tumor 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.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
See additional selected indications for KEYTRUDA in the U.S. after the Selected Important Safety Information
Selected Important Safety Information for KEYTRUDA
Severe and Fatal Immune-Mediated Adverse Reactions
KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.
Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.
Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.
Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (
