J Pharm Pharmacogn Res 2(Suppl. 1): S8, 2014
Special supplement with the abstract book of LATINFARMA 2013
CO 016: CANCER CLINICAL TRIALS: STATE OF THE ART AND THE CUBAN EXPERIENCE
Crombet-Ramos T.Center of Molecular Immunology, La Habana, Cuba.
The old paradigm for oncology drug development was based on the experience of classical cytotoxic agents. According it, antitumor activity is connected to toxicity and therefore, treatments must be scaled up to maximal tolerated dose; pharmacokinetics is relevant to define the optimal schedule; an active drug should produce rapid tumor shrinkage; the response rate is a predictor of survival and tumor progression indicates treatment failure. However, the unique characteristics of biologics challenge these dogmas and demand novel developmental guidelines. For immunotherapy, the optimal biologic dose can be far below the maximal tolerated dose, mechanisms of action can be indirect and therefore not related to pharmacokinetics, effect in survival can be seen without tumor shrinkage and therapeutic effect could be delayed in time and continue beyond progression. The new emerging paradigm recommends finding the optimal biologic dose in a “proof of principle trial” according to a pre-defined biological endpoint or biomarker; followed by an efficacy assessment in a randomized trial with long term treatment and survival as the main endpoint. CIM has now 10 projects in clinical development, including biosimilars and proprietary drugs. The original product pipeline concentrates around 3 main targets: the Epidermal Growth Factor Receptor (EGFR) system, the gangliosides and the regulatory loops of the immune system. Four of the innovative products have already transited through clinical trials and received registration in several countries: the anti-EGFR humanized monoclonal antibody nimotuzumab, the anti-CD6 antibody (itolizumab), the EGF conjugated therapeutic vaccine CimaVax-EGF and the anti-idiotypic vaccine racotumomab. The clinical experience with these products illustrates the application of the new development paradigm intended to transform cancer into a chronic disease.