How TG4010 works
TG4010 is a type of immunotherapy called a cancer vaccine. Cancer vaccines act to stimulate the immune system to recognize and target tumor cells. They are used to direct a type of immune cell, called a T-cell, to attack abnormal cells that produce a particular antigen. An antigen is a substance that is not normally produced in the body.
Many types of NSCLC and some other solid tumors express a modified version of a protein called MUC1. These modifications can be considered to be a tumor-associated antigen (TAA); they are generally unique to the cancer cells, distinguishing them from other cells in the body and making them a good target.
TG4010 is a modified virus that contains the genes for the MUC1 TAA and a cell signaling molecule called IL-2 that acts to increase the immune response in the body. The virus has been modified to render it harmless to the body. Once inside a cell, the genes contained within the virus will provide the information necessary to produce the MUC1 TAA and IL-2.
The immune system will readily recognize the virus as abnormal and take up and process the MUC1 TAA. This will trigger the production of T-cells that will specifically target tumor cells producing MUC1 protein. It is hoped that this will slow the progression of cancer and potentially reduce tumor size.
TG4010 in clinical trials
Transgene investigated the effect of TG4010 in patients with NSCLC in a Phase 2b/3 clinical trial (NCT01383148), called TIME. The trial aimed to compare the efficacy and safety of TG4010 to a placebo, alongside standard first-line chemotherapy, in 222 advanced NSCLC patients. The clinical trial took place at 72 locations in the U.S., Europe, and Israel.
The Phase 2b portion of the trial achieved its primary endpoint, which was published in the medical journal The Lancet Oncology and the trial did not proceed to the Phase 3 phase. Transgene reported that TG4010 was well tolerated and appeared safe in patients. The treatment was most effective in patients who had low levels of a particular type of immune cell, where the overall survival rate of TG4010-treated patients was 40 percent compared to only 19 percent in patients given placebo, two years after treatment.
Transgene is now investigating TG4010 in combination with other immunotherapies such as Opdivo (nivolumab) in two Phase 2 trials. Opdivo is an immune system checkpoint inhibitor, that acts to boost the immune system’s ability to recognize and target tumor cells.
The first trial (NCT02823990) is investigating TG4010 with Opdivo as a second-line therapy, once standard chemotherapy has been tried and failed to stop cancer progression. The first patient in this trial was dosed in March 2017. The trial is still seeking an estimated 33 participants at multiple U.S. sites.
In April 2017, Transgene announced a clinical research collaboration with Bristol Meyers Squibb (BMS), the developer of Opdivo. In September 2017, the U.S. Food and Drug Administration approved an investigational drug (IND) application to test the combination as a first-line therapy alongside chemotherapy in patients with NSCLC. As part of this agreement, Transgene will sponsor the Phase 2 trial and BMS will provide Opdivo to the patients. The Phase 2 trial (NCT03353675) has not yet started recruiting but aims to enroll 39 patients at multiple sites in the U.S. and Europe.
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