This article may be too technical for most readers to understand.(April 2024) |
mRNA-4157/V940 is an mRNA based cancer vaccine encapsulated in solid lipid nanoparticles. The 34 mRNA sequences in mRNA-4157/V940 vaccine were generated by an automated algorithm integrated with workflow based on massive parallel sequencing of tissue generated from cancer patients. [1] As adjuvant therapy, mRNA-4157 monotherapy and in combination with pembrolizumab have been investigated in patients with resected solid tumors (melanoma, bladder carcinoma, HPV negative HNSCC, NSCLC, SCLC, MSI-High, or TMB High cancers). It was also investigated in patients with HNSCC and MSS-CRC. [2] [3]
mRNA-4157/V940 was initially developed by Moderna starting in 2017. In May 2018, Moderna and MSD (Merck in US) announced collaboration on further development of the investigational agent. In 2019 Moderna and Merck jointly put mRNA-4157/V940 into clinical trials in combination with Merck's cancer immunotherapy drug pembrolizumab in resected stage IIIB-IV melanoma. [4] [5] [6] [7] In December 2022, Moderna and MSD announced that the study met its endpoint and demonstrated superiority. [8] In February 2023, the Food and Drug Administration granted mRNA-4157/V940 breakthrough status. [9] In April 2023, mRNA-4157 in combination with pembrolizumab received Prime Scheme Designation from the European Medicines Agency. [10]
In the 2023 AACR meeting, Professor Jeffrey S. Weber, the deputy director of the Perlmutter Cancer Center, presented the primary analysis outcome from the open-label, 2:1 randomization phase 2b study. At the pre-specified analysis point when 42 Recurrence-free survival (RFS) events occurred among 157 participants with resected stage IIIC-IV melanoma, 22.4% (24/107) in the mRNA-4157 plus pembrolizumab arm had recurrent disease, and 40% (20/50) in the pembrolizumab arm had recurrent disease, which lead to the well-known saying: mRNA-4157 in combination with pembrolizumab reduced risk by 44% in surgical resected melanoma.
In July 2023, MSD and Moderna initiated the phase III study (study V940-001) evaluating mRNA-4157 in combination with pembrolizumab for adjuvant treatment of patients with resected high-risk stage IIB-stage IV melanoma. [11]
In the meantime, a phase III study of V940 plus Pembrolizumab versus placebo plus pembrolizumab as adjuvant therapy in non-small cell lung cancer patient with resected stage II, IIIA, IIIB (N2) is registered and expected to start at November 2023. Of note, patients received prior neoadjuvant therapy for their current NSCLC diagnosis, or has been treated with any agent directed to stimulatory or coinhibitory T-cell receptor (e.g. PD-1, PD-L1, CTLA-4 , et al.) are not allowed to enrolled in the study. [12]
mRNA-4157/V940 is an mRNA based cancer vaccine. When administered, it will produce one of several dozen possible abnormal proteins commonly found in cancerous tissues. The production of those proteins is intended to invoke an immune response. mRNA-4157/V940 is given to patients after their tumors have been sequenced and abnormal proteins identified. The drug is then customized to match a patient's tumor, which makes it an example of personalized medicine.
A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.
Tecemotide is a synthetic lipopeptide that is used as antigen in an investigational therapeutic cancer vaccine. The investigational therapeutic cancer vaccine is designed to induce a cellular immune response to cancer cells that express MUC1, a glycoprotein antigen that is widely over-expressed on common cancers such as lung cancer, breast cancer, prostate cancer, and colorectal cancer. The cellular immune response may lead to a rejection of tumor tissue expressing the MUC1 antigen.
Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, immunotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.
Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for Merck Group, founded in Germany in 1668, of whom it was once the American arm. The company does business as Merck Sharp & Dohme or MSD outside the United States and Canada. It is one of the largest pharmaceutical companies in the world, generally ranking in the global top five by revenue.
CimaVax-EGF is a vaccine used to treat cancer, specifically non-small-cell lung carcinoma (NSCLC). CIMAvax-EGF is composed of recombinant human epidermal growth factor (EGF) conjugated to a protein carrier.
Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.
Moderna, Inc. is a pharmaceutical and biotechnology company based in Cambridge, Massachusetts, that focuses on RNA therapeutics, primarily mRNA vaccines. These vaccines use a copy of a molecule called messenger RNA (mRNA) to carry instructions for proteins to produce an immune response. The company's name is derived from the terms "modified", "RNA", and "modern".
Eftilagimod alpha is a large-molecule cancer drug being developed by the clinical-stage biotechnology company Immutep. Efti is a soluble version of the immune checkpoint molecule LAG-3. It is an APC Activator used to increase an immune response to tumors, and is administered by subcutaneous injection. Efti has three intended clinical settings:
Viralytics Ltd is an Australian biotechnology company working in the field of oncolytic viruses, that is, viruses that preferentially infect and kill cancer cells. The company's oncolytic virus product, called Cavatak, is currently in clinical trials in metastatic melanoma and other cancers. The drug was granted Orphan Drug status in advanced melanoma in December 2005.
Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for CDK4 and CDK6.
Epacadostat is an investigational drug for cancer. Epacadostat is an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1). Epacadostat inhibits IDO1 by competitively blocking it, without interfering with IDO2 or tryptophan 2,3-dioxygenase (TDO). It has antitumor activity in some models, though is most effective when combined with other immunotherapy agents.
Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect themselves from attack by stimulating immune checkpoint targets. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. The first anti-cancer drug targeting an immune checkpoint was ipilimumab, a CTLA4 blocker approved in the United States in 2011.
Toni K. Choueiri is a Lebanese American medical oncologist and researcher. He is the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School and Director of the Lank Center for Genitourinary Oncology at the Dana–Farber Cancer Institute. His work has led to the establishment of several novel drugs and prognostic factors in advanced renal cell carcinoma (RCC). Choueiri also co-established the International metastatic database Consortium with Daniel Heng. His biomarker work has shed light on complex immunogenomics mechanisms contributing to response and resistance to targeted therapy and immunotherapy.
Transgene S.A. is a French biotechnology company founded in 1979. It is based in Illkirch-Graffenstaden, near Strasbourg, and develops and manufactures immunotherapies for the treatment of cancer.
Autogene cevumeran is an investigational mRNA vaccine being developed jointly by BioNTech and Genentech as an adjuvant therapy in cancer treatment to prevent cancer recurrence following surgery.
Immunoliposome therapy is a targeted drug delivery method that involves the use of liposomes coupled with monoclonal antibodies to deliver therapeutic agents to specific sites or tissues in the body. The antibody modified liposomes target tissue through cell-specific antibodies with the release of drugs contained within the assimilated liposomes. Immunoliposome aims to improve drug stability, personalize treatments, and increased drug efficacy. This form of therapy has been used to target specific cells, protecting the encapsulated drugs from degradation in order to enhance their stability, to facilitate sustained drug release and hence to advance current traditional cancer treatment.