mRNA-4157 (V940) Individualized Neoantigen Therapy 2023
ModernaTX, Inc.'s mRNA novel, personalized cancer vaccine (PCV) mRNA-4157 is a therapeutic vaccine candidate combining validated defined neoantigens, predicted neoepitopes, and mutations in driver genes into a single mRNA concatemer (mRNA-4650). mRNA-4157/V940 is an investigational messenger ribonucleic acid (mRNA)-based individualized neoantigen therapy consisting of a single 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 critical step in adaptive immunity.
KEYTRUDA is an immunotherapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. Based on early clinical studies, combining mRNA-4157/V940 with KEYTRUDA may provide an additive benefit and enhance T cell-mediated destruction of tumor cells.
On November 10, 2020, Moderna issued interim data from the Phase 1 dose-expansion cohort study of mRNA-4157 combined with pembrolizumab. The data showed that mRNA-4157, combined with Keytruda®, is well tolerated at all dose levels and produced responses measured by tumor shrinkage by RECIST 1.1 criteria in HPV(-) HNSCC patients. However, no responses were observed in MSS-CRC patients. On December 13, 2022, mRNA-4157 (V940), in combination with KEYTRUDA, demonstrated a statistically significant and clinically meaningful reduction in the risk of disease recurrence or death compared to KEYTRUDA monotherapy in stage III/IV melanoma patients with a high risk of recurrence following complete resection. On January 9, 2023, the Company confirmed it plans to discuss the study results with regulatory authorities, initiate a Phase 3 clinical study in melanoma patients in 2023, and rapidly expand to additional tumor types. In addition, on February 22, 2023, Moderna and Merck announced that mRNA-4157/V940 was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the adjuvant treatment of patients with high-risk melanoma following complete resection.
Moderna announced on April 16, 2023, mRNA-4157 (V940), in combination with KEYTRUDA, reduced the risk of recurrence or death by 44% compared to KEYTRUDA alone in stage III/IV melanoma patients with a high risk of recurrence following complete resection. In addition, Moderna announced on June 5, 2023, distant metastasis-free survival (DMFS) results from the Phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study. On July 26, 2023, Merck and Moderna, Inc. announced the initiation of the pivotal Phase 3 randomized V940-001 clinical trial evaluating V940 (mRNA-4157). Global recruitment in V940-001 has begun, and the first patients are now enrolling in Australia.
An advantage of Moderna's mRNA platform is that it allows for investigational medicines that combine in a single mRNA therapy several different approaches to activate the immune system to attack cancer, either with mRNA encoding for common tumor proteins found across cancer types or multiple mRNAs encoding for various immunomodulatory proteins. In addition, personalized cancer vaccines are designed to prime the immune system so patients can generate a tailored antitumor response specific to their tumor mutation signature.
Moderna is headquartered in Cambridge, Mass.. To learn more, visit www.modernatx.com.
mRNA-4157 (V940) Indication
The mRNA personalized cancer vaccine mRNA-4157 is indicated to vaccinate patients with metastatic common epithelial cancers (melanoma). It is an mRNA-based individualized, therapeutic personalized cancer vaccine targeting 20 tumor-associated antigens expressed explicitly by the patient's cancer cells, with potential immunostimulatory and antineoplastic activities.
mRNA-4157 (V940) Dosage
In a phase 2 study, patients are vaccinated intramuscularly at 2-week intervals for (4) cycles, and dosing may be repeated for the second vaccination course.
mRNA-4157 (V940) News 2023
July 26, 2023 - “As we continue our efforts to advance novel treatment options for patients with high-risk Stage IIB-IV melanoma, the initiation of the V940-001 Phase 3 trial represents an important step forward in these efforts and our study of individualized neoantigen therapy,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “We look forward to continuing to collaborate with Moderna to evaluate this promising new approach with V940 (mRNA-4157), while also building on a standard of care laid by KEYTRUDA.”
June 5, 2023 - Kyle Holen, M.D. Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology, commented ina press release, "These results add to the emerging picture of how individualized neoantigen therapy may transform melanoma treatment and the promise it may hold for other types of cancer. Together with Merck, we are rapidly advancing our efforts to move this forward for patients."
April 16, 2023 - "Data from KEYNOTE-942 provide evidence for the potential of mRNA-4157 (V940) in combination with KEYTRUDA to improve recurrence-free survival when given to patients with resected high-risk melanoma," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. "These data support the potential of mRNA-4157 (V940) in combination with KEYTRUDA to help fight melanoma earlier and warrant investigation of the combination in a larger Phase 3 trial. We also look forward to studying mRNA-4157 (V940) and KEYTRUDA in various other early-stage cancers."
March 15, 2023 - Moderna announced that two abstracts on mRNA-4157/V940 have been accepted for presentation at the 2023 American Association of Cancer Research Annual Meeting.
February 22, 2023 - Stephen Hoge, M.D., Moderna's President, said in a press release, "mRNA-4157/V940 in combination with KEYTRUDA provided the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and potentially represents a new frontier in treating melanoma and other cancers. We look forward to publishing the full data set, sharing the results at an upcoming oncology medical conference, and continuing discussions with health authorities. We are grateful to the FDA for this designation."
December 13, 2022 - Moderna, Inc. and Merck announced that the Phase 2b KEYNOTE-942/mRNA-4157-P201 clinical trial of mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with KEYTRUDA®, Merck's anti-PD-1 therapy, demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of recurrence-free survival versus KEYTRUDA alone for the adjuvant treatment of patients with stage III/IV melanoma following complete resection. Adjuvant therapy with mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.31-1.08]; one-sided p value=0.0266) compared with KEYTRUDA alone. These results are the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial.
November 5, 2020 - Merck announced the randomized, placebo-controlled Phase 2 study investigating a 1 mg dose of mRNA-4157 in combination with pembrolizumab (KEYTRUDA®), compared to pembrolizumab alone, for the adjuvant treatment of high-risk resected melanoma is fully enrolled (n=150). The Company expects the Phase 2 data readout to occur in the fourth quarter of 2022. The primary endpoint of the Phase 2 study is recurrence-free survival at 12 months. The Phase 1 in multiple cohorts is ongoing, and the expanded head and neck cohort is recruiting additioCompany'snts.
November 11, 2020 - Moderna, Inc. shared interim data fromMerck'spansion cohort of its ongoing Phase 1 study of the Cancer mRNA personalized cancer vaccine (PCV) mRNA-4157 combined with Merck's Keytruda® at The Society for Immunotherapy of Cancer's Annual Meeting. The data shared today showed that mRNA-4157 given in combination with Keytruda® is well tolerated at all dose levels and produced responses as measured by tumor shrinkage by RECIST 1.1 criteria in HPV"-) HNSCC patients.
November 9, 2020 - A clinical trial at the University of Arizona Health Sciences designed to study the safety and effectiveness of a personalized cancer vaccine in combination with the immunotherapy drug Pembrolizumab will expand its cohort after promising preliminary data were presented at the annual meeting of the Society for the ImmunotMerck'sof Cancer.
June 1, 2019 - The data showed that the mRNA personalized cancer vaccine mRNA-4157, given alone or combined with Merck's pembrolizumab (KEYTRUDA®), was well-tolerated at all doses tested and elicited neoantigen-specific T-cell responses. No vaccine-related serious adverse events were reported for the PCV when administered to patients as a monotherapy or combined with pembrolizumab.
December 13, 2016 - Moderna announced 'We are developing an mRNA-based personalized cancer vaccine (PCV) with the potential to prime the immune system to recognize cancer cells and mount a strong, tailored response to each patient's cancer."
mRNA-4157/V940 Clinical Trials
Clinical Trial NCT03313778: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects With Resected Solid Tumors and Combination With Pembrolizumab in Subjects With Unresectable Solid Tumors (KEYNOTE-603Thishis phase 1 studies is to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and combination with pembrolizumab in subjects with unresectable solid tumors.
Clinical Trial NCT03897881: An Efficacy Phase 2 Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Patients With High-Risk Melanoma (KEYNOTE-942). The purpose of this Phase 2 study is to assess whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence-free survival (RFS) compared to pembrolizumab alone in patients with complete resection of cutaneous melanoma and a high-risk of recurrence.
The results of this ongoing study were announced on December 13, 2022. More information about this study and its results can be found here.