How TG4010 works
Some cells have a protein called MUC1 on their surface. This protein is modified in cancer cells, making it a highly immunogenic tumor-associated antigen. This means the immune system detects these abnormal modifications as foreign, and attacks cells showing MUC1 alterations.
TG4010 is a modified vaccinia virus Ankara (MVA) that expresses the MUC1 antigen and the cytokine Interleukin-2 (IL2), activating the innate and adaptive immune system toward MUC1-positive cancer cells. IL2 is a cytokine, a naturally occurring protein that boosts the activity of the immune system.
TG4010 in clinical trials
Transgene, a French pharmaceutical company, reported positive results in 2014 and 2015 from the Phase 2b study (NCT01383148). This was a randomized, placebo-controlled study that aimed to evaluate TG4010 in combination with chemotherapy (active group) compared to placebo plus chemotherapy (control group) as a first-line treatment for MUC1-positive advanced NSCLC.
The study’s primary aim was to show an improvement of progression-free survival after six months of treatment. It also aimed to validate a biomarker, the TrPAL (Triple Positive Activated Lymphocytes), which had been discovered in a previous study, for efficacy.
The analysis compared progression-free survival in the two groups according to the patient’s TrPAL levels (high or normal). TG4010 in combination with chemotherapy showed improvement of survival after six months of treatment in 43.2 percent of patients who received TG4010 and chemotherapy. Moreover, results showed an association between survival and TrPAL levels, with patients having high TrPAL levels suffering lower survival rates.
Overall, TG4010 was well tolerated, and the most frequent side effects were mild to moderate reactions at the site of injection.
In March 2017, Transgene announced the initiation of a Phase 2 clinical trial (NCT02823990) evaluating TG4010 in combination with Opdivo (nivolumab) for the treatment of metastatic NSCLC patients who have failed one prior line of platinum-based chemotherapy.
The multicenter, open-label study has a primary endpoint of overall response rate, defined as the proportion of patients who achieved a partial or complete response to treatment. Secondary endpoints include progression-free survival, overall survival, duration of response and safety. The company expects to enroll 33 patients in this study. TG4010 will be administered under the skin at a dose of 108 pfu weekly for six weeks and every three weeks thereafter. The first results are expected by the end of 2017.
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