Moderna and Merck Report Five-Year Data Showing Sustained Improvement in Recurrence-Free Survival with Intismeran Autogene Plus KEYTRUDA® in High-Risk Stage III/IV Melanoma Patients After Complete Resection
Moderna, Inc. and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced median five-year follow-up data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study, evaluating intismeran autogene (mRNA-4157 or V940), an investigational mRNA-based individualized neoantigen therapy (INT), in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with high-risk melanoma (stage III/IV) following complete resection.
In this pre-planned analysis, adjuvant treatment with intismeran autogene in combination with KEYTRUDA continued to demonstrate sustained and clinically meaningful improvement in the study’s primary endpoint, recurrence-free survival (RFS), reducing the risk of recurrence or death by 49% (HR=0.510; [95% CI, 0.294–0.887]; one-sided nominal p=0.0075) compared to KEYTRUDA alone. Moderna and Merck plan to present further data from follow up analyses of primary and secondary endpoints at an upcoming medical meeting.
“Now with five years of follow-up data, today’s results highlight the potential of a prolonged benefit of the intismeran autogene and KEYTRUDA combination in patients with resected high-risk melanoma,” said Kyle Holen, M.D., Moderna’s Senior Vice President and Head of Development, Oncology and Therapeutics. “We continue to invest in our platform in oncology because of encouraging outcomes like these, which illustrate mRNA’s potential in cancer care. We look forward to several additional milestones to come, including the results of our Phase 3 study in adjuvant melanoma in collaboration with Merck, and continued progress across the eight Phase 2 and Phase 3 studies in multiple tumor types and patient populations.”
“For many patients with stage III/IV melanoma, there is a significant risk of recurrence following surgery. As such, demonstrating the longer-term potential of intismeran autogene and KEYTRUDA to reduce the risk of recurrence for certain patients with melanoma is a meaningful milestone,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “These five-year follow up data are encouraging and we look forward to late-stage data from the INTerpath clinical development program with Moderna, across a range of tumor types where significant unmet needs remain.”
This analysis from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study (NCT03897881)builds on the primary analysis conducted at approximately two years of follow up,Merck as well as a subsequent analysis at three years of follow up. The safety profile of intismeran autogene in combination with KEYTRUDA in the study remains consistent with that previously reported.
In collaboration with Merck, the Phase 3 clinical trial for adjuvant melanoma (INTerpath-001, NCT05933577) is fully enrolled. Two non-small cell lung cancer (NSCLC) Phase 3 studies, evaluating adjuvant treatment in patients with completely resected NSCLC and evaluating adjuvant treatment for patients with resectable NSCLC after receiving neoadjuvant KEYTRUDA plus platinum-based chemotherapy, are enrolling. The randomized Phase 2 study for adjuvant renal cell carcinoma is fully enrolled. Randomized Phase 2 studies for patients with resected muscle invasive and resected non-muscle invasive bladder cancer are enrolling, a Phase 2 study of first-line treatment for patients with metastatic melanoma and a Phase 2 study of first-line treatment for patients with metastatic squamous NSCLC are also enrolling.
About intismeran autogene (mRNA-4157 or V940)
Intismeran autogene 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 Merck 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.
About KEYNOTE-942/mRNA-4157-P201 (NCT03897881)
KEYNOTE-942 (The Lancet, Volume 403, Issue 10427, 632 – 644) is an ongoing randomized, open-label Phase 2b trial that enrolled 157 patients with high-risk stage III/IV melanoma. Following complete surgical resection, patients were assigned 2:1 (stratified by stage) to receive intismeran autogene (1 mg every three weeks for nine doses) and KEYTRUDA (200 mg every three weeks up to 18 cycles [for approximately one year]) versus KEYTRUDA alone for approximately one year until disease recurrence or unacceptable toxicity.
The primary endpoint is RFS, defined as the time from first dose of KEYTRUDA until the date of first recurrence (local, regional or distant metastasis), a new primary melanoma, or death from any cause in the intention-to-treat population. Secondary endpoints include distant metastasis-free survival and safety, and exploratory endpoints include distribution of TMB expression in baseline tumor samples across study arms and their association with the primary RFS endpoint.
Key eligibility criteria for the trial included: patients with resectable cutaneous melanoma metastatic to a lymph node and at high risk of recurrence, patients with complete resection within 13 weeks prior to the first dose of KEYTRUDA, patients were disease free at study entry (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases, patients had a formalin fixed paraffin embedded (FFPE) tumor sample available suitable for sequencing, Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 and patients with normal organ and marrow function reported at screening.
About melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with more than 330,000 new cases diagnosed worldwide in 2022. In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be over 100,000 new cases of melanoma diagnosed and over 8,000 deaths resulting from the disease in the U.S. in 2025.
About KEYTRUDA® (pembrolizumab) injection for intravenous use, 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.
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