Mirror Biologics and Merck KGaA Partner on Metastatic Colorectal Cancer Trial

Mirror Biologics, Inc., a company specializing in immunotherapy products using living, non-genetically altered, allogeneic immune cells, has announced a new collaboration with Merck KGaA, Darmstadt, Germany. This partnership aims to conduct a Phase II clinical trial to evaluate the effectiveness of combining an experimental immunotherapy drug, AlloStim®, developed by Mirror, with an immune checkpoint inhibitor (ICI), avelumab (BAVENCIO®), from Merck KGaA. The trial, identified as NCT06557278, will focus on patients with fourth-line metastatic colorectal cancer.

Colorectal cancer (CRC) is currently the third most diagnosed cancer and ranks as the second highest cause of cancer-related deaths worldwide. In 2023, around 153,020 cases of CRC were diagnosed in the United States, leading to 52,550 deaths. Globally, 2020 saw over 1.9 million new cases and approximately 900,000 deaths from CRC. The incidence of this cancer is increasing, with projections estimating that the number of CRC cases worldwide could rise to 2.5 million by 2035. This highlights a critical need for new treatment options that can improve both life expectancy and quality of life for patients with advanced metastatic CRC.

ICI drugs have transformed the treatment landscape for several solid tumors by improving prognosis. These drugs are particularly effective against tumors known as immunologically ‘hot,’ which are characterized by high numbers of infiltrating anti-tumor immune cells. Unfortunately, most solid tumors, including nearly all CRC tumors, are classified as immunologically ‘cold,’ meaning they lack infiltrating immune cells and do not respond well to ICI therapy. The goal of this collaboration is to test whether the experimental AlloStim® can transform CRC tumors into ICI-responsive ones, potentially offering a new therapeutic avenue for patients.

Previous evidence supporting this approach comes from a rare case where the combination of AlloStim® and ICI resulted in an objective tumor response in a patient with metastatic CRC. This has motivated further exploration of this therapeutic combination. Dr. Michael Har-Noy, Founder and Chief Medical Officer of Mirror Biologics, expressed enthusiasm for the partnership, noting the limited treatment options available for patients with advanced metastatic CRC. The collaboration with Merck KGaA could unveil new possibilities for these patients by investigating combination therapies.

Mirror Biologics will sponsor the clinical study, while Merck KGaA will supply avelumab. The open-label Phase II study plans to enroll up to 50 patients with metastatic CRC who have not responded to chemotherapy or immunotherapy and have failed at least one third-line, non-chemotherapy treatment. The trial will be conducted across approximately 10 sites in the United States.

Avelumab, a human anti-programmed death ligand-1 (PD-L1) antibody, has demonstrated its ability in preclinical models to activate both adaptive and innate immune responses. By blocking PD-L1 receptors, it releases the suppression of T cell-mediated antitumor immune responses. Furthermore, avelumab has shown potential in inducing NK cell-mediated tumor cell destruction through antibody-dependent cell-mediated cytotoxicity in vitro. In the U.S., avelumab is approved in combination with axitinib for the first-line treatment of advanced renal cell carcinoma and as a monotherapy for certain types of metastatic cancers.

Mirror Biologics, Inc. is a private corporation based in Delaware, with comprehensive operational facilities in Tampa, Florida. The company also has manufacturing operations in Jerusalem, Israel, and additional clinical operations in Thailand and Malaysia. Its lead product, AlloStim®, is an "off-the-shelf" non-genetically modified immune cell therapy protected by over 200 patents. AlloStim® is currently undergoing multiple clinical trials for various indications, including metastatic colorectal cancer and advanced liver cancer. It is also being tested in a trial involving older adults to counteract age-related immune decline and provide broad respiratory viral protection.