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Trial Underway Testing Personal RNA Cancer Drug

Cancer in headline


15 November 2017. A clinical trial is underway testing a treatment for solid tumor cancers derived from messenger RNA, genetic material with protein coding instructions for cells. The trial is conducted by biotechnology company Moderna Therapeutics in Cambridge, Massachusetts, testing the safety of its experimental drug code-named mRNA-4157 both by itself and with the immunotherapy drug pembrolizumab, marketed by drug maker Merck as Keytruda.

Moderna develops therapeutic proteins with a technology that synthesizes messenger RNA, a nucleic acid with the genetic code from DNA used by cells to produce the amino acids in proteins for cellular functions. Moderna manipulates the coding region in the messenger RNA chemistry to provide instructions for cells to produce proteins with specific therapeutic properties. Those coding instructions are contained in a standard package that appears in most cases like natural RNA to avoid triggering an immune response, and reach the desired cells where the therapeutic protein is needed.

Moderna’s mRNA-4157 is an exception to its general technology platform, in that it’s designed to provoke an immune response. In this case, the immune response attacks targets called neoantigens, unique sets of mutations expressed in cancer patients’ tumors. Thus mRNA-4157 is expected to act like a vaccine to induce immune responses specifically targeted to those unique mutations, addressing 20 specific regions on the neoantigen targets.

In June 2016, as reported in Science & Enterprise, Moderna began a collaboration with drug maker Merck to develop a messenger RNA drug to enhance the capabilities of Keytruda that harnesses the immune system to fight tumors. Keytruda is in a class of drugs called checkpoint inhibitors that limit the actions of tumor cells to block the immune system. In this case, Keytruda stops receptor proteins on the surface of tumor cells from blocking the activation of T-cells in the immune system to attack tumors. Keytruda is already approved by Food and Drug Administration to treat a number of solid tumor and blood-related cancers.

The clinical trial is mainly testing the safety of mRNA-4157 for 21 days, but also looking for any evidence of anti-tumor activity over 50 days. The early-stage study is enrolling 90 individuals at 6 sites in the U.S. with a variety of solid-tumor cancers, such as lung cancer and melanoma, that cannot be removed by surgery. Participants will be assigned to receive mRNA-4157 at various dosage levels, to find the maximum tolerated dose, both alone and when combined with Keytruda, as well as among patients with different types of tumors.

The research team is also tracking the ability of mRNA-4157, either with or without Keytruda, to generate antigen-specific T-cells, as well as gauge any effects on biomarkers specific to the tumors in patients. The study is likewise measuring among Keytruda recipients the concentration of the drug in their blood, as well as any antibodies countering the effects of Keytruda. In addition, researchers are tracking response rates to the drugs in the patients’ tumors, as well as overall and progression-free survival time.

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