Description
TG4010 is in development for the treatment of metatstatic non small cell lung cancer (NSCLC), in combination with first line chemotherapy.
TG4010 is based on a recombinant vaccinia virus expressing the MUC1 antigen and the human cytokine, Interleukin-2 (IL2). TG4010 is meant to induce both innate and adaptive immune responses. The MUC1 protein is a highly glycosylated mucin normally found at the apical surface of epithelial cells in many types of tissue. In tumor cells, several modifications of MUC1 occur: over expression, hypoglycosylation and changes in cellular localization. These changes make MUC1 an attractive target for 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 adaptive immunity.
Medical Need
Lung cancer is one of the most common malignancies worldwide with an incidence of 1.35 million people and is the leading cause of cancer-related deaths, accounting for some 1.2 million deaths in 2002. NSCLC represents approximately 80 per cent of all lung cancers. Some 41 per cent of NSCLC are already metastatic at diagnosis and the rest become metastatic during the course of the disease. Current treatments for lung cancer include surgery, chemotherapy, radiation and targeted molecular therapy but only one third of patients present resectable (able to be removed by surgery) disease at diagnosis. The poor prognosis in patients with advanced disease is improved by palliative platinum-based chemotherapies that produce longer survival times. However, the medical need for developing new treatments for NSCLC remains extremely high and new approaches are necessary to significantly change the outcome of the disease. By modifying the host/tumor relations, immunotherapy products like TG4010 may achieve such a result.
There is potential for TG4010 to treat earlier stages of NSCLC, as well as other solid tumors expressing MUC1, such as prostate, breast, pancreas and colorectal cancers.
Clinical Development
The efficacy and safety of TG4010 have been assessed in a randomized, controlled Phase IIb study evaluating the therapeutic vaccine TG4010 as an adjunct to standard chemotherapy in 148 patients with advanced NSCLC. The primary objective of the study was met (Progression free survival at 6 months of at least 40% in the experimental arm). For the latest clinical trial data see the press releases on TG4010.
During the phase IIb trial, Transgene identified a subpopulation of patients who particularly benefited from the treatment with TG4010 and chemotherapy, versus chemotherapy alone. This sub-population consisted of patients with normal levels of activated NK cells (natural killer cells) at baseline and represented some 73 per cent of the evaluable patient population (101 out of 138 patients). The phase IIb clinical results have demonstrated an improved clinical outcome for patients in this subpopulation with a statistically significant 6 month increase in median survival (17.1 months in the experimental arm versus 11.3 months in the control arm). Response rate, time to progression and progression free survival data also confirmed the identification of activated NK cells as an appropriate predictive biomarker associated with the positive clinical outcome for patients with NSCLC treated with TG4010 in combination with chemotherapy.
A pivotal, global, controlled phase IIb/III trial of TG4010 in patients with adavanced stage (IV) NSCLC is expected to begin in the fourth quarter of 2010. The trial will involve the overall recruitment of 1000 patients with MUC-1 positive NSCLC and normal levels of activated NK cells at baseline.
Collaborative Program
In 2009 Transgene was awarded, as part of the ADNA program, funds of up to €18.4million from the French innovation agency, OSEO, for the research and development of biomarkers that will enable new therapies to be prescribed to patients that will actually benefit from them. The objective is to be able to prescribe the right drug to the right patient. The identification of normal levels of activated NK cells at baseline, as a predictive biomarker in the phase IIb TG4010 trial, is a consequence of this important and ongoing collaborative program.
Corporate Partnership
In March, 2010 Transgene signed an exclusive option agreement with Novartis for the development of TG4010 across multiple cancer indications. See the press release of March 10, 2010.
Related press releases :
