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TG4010, a novel MUC1 targeting immunotherapy, is in development for the treatment of metastatic non-small cell lung cancer (NSCLC) in combination with first-line chemotherapy.
TG4010 is a recombinant vaccinia virus of the Ankara strain (MVA) expressing the coding sequences of the MUC1 antigen and of the cytokine, Interleukin-2 (IL2). In healthy cells, the MUC1 protein is normally found on the surface of epithelial cells in many types of tissue and works to protect these cells. In tumor cells, several modifications of MUC1 can occur: over expression, hypo-glycosylation and changes in cellular localization. These changes transform the MUC1 protein into a highly immunogenic tumor associated antigen (TAA) and make it an attractive target for cancer immunotherapy. Thus, the strategy is to induce MUC1 antigen expression in a non-tumor environment, i.e., where the immune system is fully functional, in order to induce both innate and MUC1 specific adaptive immunity. In addition to lung cancer, the MUC1 TAA is expressed in many other solid tumor types, such as breast, colorectal, kidney and prostate cancers.
Via Krishan Maggon
The safety and activity of TG4010 have been evaluated in Phase 1 and 2 studies in several types of solid tumors. TG4010 is currently in late-stage clinical development for the treatment of advanced MUC-1 positive NSCLC.
In 2014, Transgene reported results from the Phase 2b part of the Phase 2b/3 TIME trial evaluating TG4010 in combination with chemotherapy in patients with Stage IV NSCLC. The primary objective of the Phase 2b part of the trial was to validate a predictive biomarker for efficacy that was identified in an earlier Phase 2 trial (TG4010.09) in NSCLC. The results of both the Phase 2b part of the TIME trial and the TG4010.09 trial are discussed below.
The improvements in PFS and OS in this non-squamous population were even more notable in the so-called “low” TrPAL group of patients; the low TrPAL group is similar to the normal TrPAL group but with a slightly lower TrPAL cell threshold level corresponding to the 75% of patients with the lowest values.
TG4010 was well tolerated, and the nature and incidence of adverse events in the TG4010 arm were consistent with previous Phase 2 clinical trials. The most frequent TG4010-related adverse events were mild to moderate injection site reactions.
The Company is moving forward with preparations for the Phase 3 part of the TIME trial, which is planned to enroll only patients with non-squamous disease. Transgene is seeking a global development and commercialization partner for TG4010 and talks are ongoing with potential partners.