On October 12, 2017 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage oncology biotechnology company, reported that the Company has been included in the SU2C CatalystTM program, a cutting-edge research initiative led by Stand Up To Cancer (SU2C) designed to bring innovative cancer treatments to patients quickly through novel collaborations between industry and academia (Press release, Mirati, OCT 12, 2017, View Source [SID1234520918]).
A clinical trial research grant has been awarded to the Van Andel Research Institute (Grand Rapids, Michigan) to evaluate the potential of epigenetic agents to improve patient responses to immunotherapy in non-small cell lung cancer (NSCLC). The $2.5 million research grant will support a Phase 1/1b study combining Mirati’s mocetinostat, an orally-bioavailable, spectrum-selective Class 1 & IV HDAC inhibitor, guadecitabine, a DNA methyltransferase (DNMT) inhibitor from Astex, and pembrolizumab, a PD-1 checkpoint inhibitor from Merck (known as MSD outside the U.S. and Canada). The grant is provided by Merck, a SU2C Catalyst Founding Supporter.
“We are honored to participate in this ground-breaking trial with pembrolizumab and guadecitabine. The combination of immunotherapy with epigenetic agents such as mocetinostat has great potential to positively impact outcomes for patients with NSCLC,” said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer. “The SU2C Catalyst program is an exceptional example of a collaboration designed to benefit cancer patients in an unprecedented way.”
The team is led by Stephen Baylin, M.D., and Matthew Hellmann, M.D. Dr. Baylin is the co-director of the Cancer Biology Division and associate director for research programs for Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins as well as the co-leader of the VARI-SU2C Epigenetics Dream Team while Dr. Hellmann is an oncologist at Memorial Sloan Kettering Cancer Center in New York. Memorial Sloan Kettering will coordinate the trial with Dr. Hellmann as principal investigator.
“Despite the current and exciting advances with immune checkpoint therapy, many patients with NSCLC still do not receive benefit and this continues to be an extremely challenging disease. However, we remain optimistic that with continued research on the immune modulatory effects of epigenetic agents, the ability to test the hypothesis in trials like this, that these drugs combined with immune checkpoint therapy will contribute to improved ways to treat patients with NSCLC,” said Dr. Baylin.
The trial is now open and enrolled its first patient in August 2017. Additional information on the trial can be found at View Source For information on SU2C Catalyst and this project, visit SU2C.org.
Mirati is also conducting a Phase 2 study of mocetinostat in combination with durvalumab in NSCLC patients who have experienced progression of disease after treatment with checkpoint inhibitor therapy. Patients are stratified into two cohorts based upon their best response to prior checkpoint therapy. Stage 1 of the study is currently enrolling nine patients in each cohort; one cohort has already met the prespecified criteria for expansion into stage 2 with at least one confirmed partial response. Mirati will provide an update on this study by the end of the year.
About Mocetinostat (MGCD103)
Mocetinostat (MGCD103) is an orally-bioavailable, spectrum-selective Class I & IV HDAC inhibitor. Class I HDAC inhibition of histone acetylation is predicted to enhance the recognition of tumor cells by anti-tumor T cells and reverse immunosuppressive factors in the tumor microenvironment. Epigenetic immunomodulation may enhance immune response to tumors, and ultimately improve patient response to immunotherapies. Mocetinostat is being studied in a Phase 2 trial as a combination therapy with durvalumab, targeting the programmed death ligand 1 (PD-L1) pathway, which has been implicated in advanced lung cancers.
Mirati retains worldwide rights to mocetinostat except for certain Asian territories where the program is partnered with Taiho.