Date: 2016-11-04
Type of information: Results
phase: preclinical
Announcement: results
Company: Onxeo (France)
Product: Livatag® (doxorubicin Transdrug®)
Action
mechanism: antineoplastic antibiotic. Livatag® (Doxorubicin Transdrug™) is a doxorubicin formulation in the form of lyophilized nanoparticles of polyisohexylcyanoacrylate (PIHCA).This new therapeutic approach allows drug resistance to be avoided by shortcircuiting the mechanisms of multi-drug resistance developed by tumor cells through the masking of the anticancer agent. Acting as a ‘Trojan horse,’ the nanoparticle formulation avoids rejection of doxorubicin outside the cell so that it can exert its cytotoxic action. By specifically targeting tumor cells in the liver and overcoming resistance to doxorubicin, Livatag® represents a significant breakthrough in the treatment of this cancer. Livatag® is currently being evaluated clinically as a monotherapy in a Phase III Relive trial for second-line advanced hepatocellular carcinoma. More than 90% of expected patients have been randomized and study preliminary data are expected mid-2017.
Disease: pancreatic cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On November 4, 2016, Onxeo announced results from a series of preclinical studies evaluating Livatag® interest for pancreatic cancer. The company has initiated an exploratory preclinical evaluation program of Livatag® for new indications, such as pancreatic cancer, which is part of Onxeo’s strategic efforts to capitalize on the specific benefits of the drug and the acquired knowledge of its mechanism of action. A first set of preclinical studies has been performed and confirmed several key advantages of Livatag® versus free doxorubicin: Livatag® demonstrated on average a two-fold increase in potency compared to free doxorubicin when tested on a range of pancreatic cell lines. Additionally, Livatag® significantly extended the plasma life-time of the active ingredient doxorubicin compared with conventional formulation of free doxorubicin.
In murine pancreatic cancer models where free doxorubicin had limited effect, Livatag® exhibited good, dose-dependent efficacy. Similar to results previously shown in HCC, these preclinical studies showed that Livatag® has good exposure in pancreatic tumors without increasing exposure in other vital organs such as heart and lungs, when compared to free doxorubicin. This study in murine orthotopic pancreatic cancer models also demonstrated, similarly to previous observations with Livatag® in HCC models, that Livatag® in combination with checkpoint inhibitors resulted in supra-additive efficacy.
Following the initial mechanisitic and pharmacokinetic/pharmacodynamic data, the company intiated a study plan to assess the effect of Livatag® in comparison with current standard treatments, either in monotherapy or in combination to assess how these first data might translate into the clinical setting to validate the potential interest of Livatag® in this indication. In a mouse syngeneic pancreatic cancer model, Livatag® as a monotherapy proved to be as effective or more effective than current therapies, including chemotherapies gemcitabine, paclitaxel, and erlotinib. In addition, the study demonstrated that Livatag® combines well with these three therapies, showing good tolerance and exhibiting supra-additive efficacy in all combinations compared to each agent alone.
