The treatment of cancer in general, and especially in those more aggressive types of cancer, consists of combinations of drugs with different mechanisms of action, in order to eliminate all cancer cells. The main problem with these therapies is that in the long run, most patients end up becoming resistant and refractory to therapy. Therefore, it is important to develop new therapies and, in particular, the development of new combination therapies based on different mechanisms of action and that act on different cell targets, and that aim to reduce the appearance of resistance phenomena. With the general objective of demonstrating the effectiveness of a combination treatment aimed at cancer patients with important unmet medical needs, as well as developing tools and biomarkers that reduce the risk of their future clinical development, the present COMBO-EPOC project has been proposed with the following specific objectives: Objective 1: Demonstrate the safety and efficacy of combined ORY-1001 treatment with SOC treatments in a clinical setting, by conducting two Phase IIa Concept Test studies in AML and SCLC patients. Objective 2: Improve the repertoire of in vitro and in vivo models to optimise in the same experimental model the evaluation of drugs with different mechanisms of action and aimed at the treatment of cancer, and explore in them new synergistic combinations with the ORY-1001. Objective 3: Validate the use of two pre-selected biomarkers for SCLC patient stratification as predictor markers of ORY-1001 response to ORY-1001 Objective 4: Identify and characterise new pharmacodynamic biomarkers useful for stratification or monitoring of patients, predictors of the progression of the pathology or response to treatment, etc. This project involves the integration of the experience of the partners of the Consortium in the various aspects of it. Thus, Oryzon brings his experience in the pharmaceutical development of ORY-1001, epigenetic modulation and the development of biomarkers. VHIO and IISLaFe are two health institutions of great national and international prestige and their experience in the development of clinical studies will be of great importance for the design and execution of the PoC studies foreseen in the project. In addition, both institutions are well aware of the benefits of ORY-1001 treatment of patients affected by AML or SCLC, and are characterised by combining this clinical experience with the development of translational and preclinical studies of interest to the project. Finally, LEITAT will put at the service of the project its extensive experience as an expert technological center in the development of experimental models. The duration of the project is estimated at 36 months (start 01/01/2018 and end 31/12/2020) and has been divided into 4 work packages: WWP1. Combination studies and mechanism of action WWP2. Biomarkers WWP3. Clinical studies WWP4. Management and exploitation of the project The overall budget of the project presented is estimated at 1,703,299, thus exceeding the 500,000 required by the call. The budget of Oryzon Genomics amounts to 1,125,076 corresponding to 66 % of the total budget, VHIO (179,519) and LEITAT (145,477o) and IISLaFe (223.227) represent 11, 10 and 13 % of the budget each of them respectively. Therefore, the distribution of the budget among the various participants complies with the rules of the call where none of the participants has more than 75 %, the budget in the hands of the companies is more than 60 % and none of the participants have a participation less than 10 %. Thus, the amount eligible for the project amounts to a total of 1,641,629.