Few companies have the legacy and global reach of the pharmaceutical giant Merck. Formed in 1668, the company has grown to become one of the world’s largest and most respected pharmaceutical corporations, producing drugs to treat everything from malaria and heart disease to diabetes and cancer.
Now, with a range of blockbuster products and clinical trials proving their worth, Merck is looking to revolutionize cancer therapy once again. This time, they’re focusing on immunotherapy—or the use of our immune system to attack cancer—with their new drug, MRK-TRIO. If the FDA approves it, the treatment could become the newest blockbuster on the market.
Why Immunotherapy Works: Key Facts
Cancer is among the leading causes of death worldwide. In the U.S., it is estimated that there will be about 1 in 3 people diagnosed with cancer this year. While there are different treatments for cancer, there is still no cure. That’s because cancer typically develops over the course of many years, and while existing drugs can help, they don’t cure the disease.
For years, medical professionals have known that our bodies have the ability to recognize and destroy cancer cells. Immunotherapy is just the latest attempt by scientists to harness this ability and use it to fight disease.
As with other forms of cancer therapy, the idea behind immunotherapy is to provoke the body’s immune system to fight the tumor. The difference is that instead of using chemicals or radiation to do this, geneticists reprogrammed cells to recognize cancer and kill it. This technique allows doctors to target specific cancers with fewer side effects. It also means that the treatment could potentially work for people who have already been exposed to the disease or its treatment. For instance, those previously treated for Hodgkin’s or non-Hodgkin’s lymphoma couldn’t benefit from existing therapies, but could from a cancer vaccine.
The Evolution of Immunotherapy
The idea of immunotherapy is as old as modern medicine itself. In 1931, Scottish surgeon James Beattie performed the first human implantation of a tissue graft, which prompted an immune system response that destroyed the cancerous tissue. Since then, scientists and doctors have been searching for a way to harness this immune response and use it to fight disease. It was not until the late 1990s that modern immunotherapy really took off, with scientists discovering that certain genes were responsible for causing cancer, and that these genes could be used to generate powerful immune responses. This led to the development of genetically modified vaccines, which combine genetic material from weakened or killed viruses with components from cancerous cells, and are designed to prompt the body’s immune system to fight the cancerous tissue. These vaccines are currently used to treat several types of cancer, including renal cell carcinoma, non-Hodgkin’s lymphoma, and glioblastoma.
Revolutionizing Immunotherapy
One of the world’s largest pharmaceutical companies, Merck has invested heavily in research and development to create the next generation of cancer treatments. Working with scientists at their labs and clinical centers around the world, they have developed a new treatment for acute myeloid leukemia (AML), a type of cancer that affects the blood and bone marrow. Known as MRK-TRIO, the treatment aims to harness the body’s immune system to fight the cancer. It does this by enhancing the activity of specific white blood cells known as NK cells, which attack and digest foreign substances like bacteria and viruses. Cancer cells, on the other hand, are generally ‘invisible’ to the immune system, so it will not recognize them as ‘foreign’ and therefore attack them. By infusing patients’ blood with a compound that enhances NK cell activity, Merck hopes to see some positive results from their clinical trials.
A Closer Look At MRK-TRIO
To understand how MRK-TRIO works, it is important to know a little bit about its components. First, the medication is a combination of two existing drugs, monomethyl auristatin E (MMAE) and aflibercept (also known as VEGF-trap). MMAE is a substance that interferes with the growth of cancer cells; it prevents their attachment to other cells or tissues. The second drug, aflibercept, is aflibercept binds to a protein called VEGF, which prevents it from signaling to other cells. Signaling refers to a process in which cells send messages to each other, resulting in the development and growth of new tissues. In the case of cancer, VEGF promotes the growth of new blood vessels (vasculogenesis) within tumors, making them bigger and helping them to spread to other parts of the body. Inhibition of VEGF reduces the growth of new blood vessels within tumors, making them smaller. Consequently, tumors become less aggressive and more susceptible to existing treatments.
The two drugs, aflibercept and MMAE, were originally developed separately, but when combined offer significant advantages. First, because they are both anti-angiogenic agents, they work synergistically to reduce tumor growth. Second, because they work by different mechanisms, combining them offers the potential to target more cells and grow them resistant to the drugs. Last but not least, aflibercept is a more potent inhibitor of VEGF than MMAE, so by combining the two drugs, we are essentially getting the best of both worlds. The end result of all these advantages is that MRK-TRIO has the potential to treat cancers more effectively than ever before.
The phase I/II trial was designed to assess the safety and efficacy of MRK-TRIO in patients with AML, and the results were published recently in the New England Journal of Medicine.
Most Promising New Treatment For Cancer
There are several promising new drug treatments for cancer appearing in research labs and early-stage clinical trials that could be the next big thing. Here are some that caught our attention.
NCT03024926
This is an open-label, single-arm, phase II trial that seeks to investigate the safety and efficacy of an agonistic anti-CD40 monoclonal antibody (rituximab) in combination with a chemotherapy agent (gemcitabine) in patients with advanced solid tumors. In 2017, rituximab was approved by the FDA for use in combination with Gemcitabine (Gemzar) for the treatment of relapsed or refractory non-Hodgkin’s lymphoma. Antibodies are proteins produced by the bodies that aid in the recognition and destruction of foreign invaders (namely, cells that have become cancerous). In this way, rituximab acts like a keystone: it helps prevent tumors from developing by recognizing and attacking cancerous cells before they can grow and spread to other parts of the body. This makes it a perfect candidate for combination therapy with Gemcitabine. The main purpose of this trial is to see how well rituximab works in combination with Gemcitabine in patients with advanced solid tumors, and to confirm its safety and tolerance in this population. The trial has already recruited over 70 patients, and it is currently in the middle of recruiting participants. Results are expected in the coming months.
NCT01693594
This is a phase I/II trial that will examine the safety and effectiveness of an antisense oligonucleotide targeting the COX-2 gene in patients with malignant pleural mesothelioma. This type of mesothelioma is a cancer that affects the membranes that line the lungs and other organs. It is associated with asbestos exposure, and the trial looks to assess the effectiveness of the antisense oligonucleotide in reducing tumor volume and increasing patient survival. The trial is recruiting participants, and results are expected in 2021.