Objective Colorectal cancer (CRC) is increasingly being recognized as a heterogeneous disease with distinct molecular subtypes. These subtypes have different biological processes at the basis of their disease and consequently their prognosis and responses to therapy are also different.We have previously developed molecular diagnostic assays using a single platform on routine FFPE tumour biopsies. These assays identify gene expression profiles with distinct prognosis and drug response phenotypes (CMS4/c-type, BRAF mutant-like, and MSI-like). Our overall objective is to develop targeted therapies more effective than the current therapies that do not take advantage of molecular classification of the disease to select patients for therapy. We therefore propose to perform 3 two-stage single arm multi-centre open-label phase II studies based on solid preclinical evidence and a sound scientific rationale for these subgroups of CRC patients: 1) combination of chemotherapy and a TGF-βR inhibitor (LY2157299) in patients presenting a C-type signature; 2) vinorelbine in patients with a BRAFm-like signature; and 3) an immunotherapeutic anti-PD-L1 drug (MPDL3280A) in combination with bevacizumab in patients with a MSI-like signature. The primary objectives of these studies are to determine the clinical efficacy (progression-free survival as primary endpoint), safety and tolerability of the experimental treatments in these molecularly selected populations. Mutation analysis at the beginning of treatment and monitoring by liquid biopsies might reveal further biomarkers that predict response in retrospective analysis.The project outcomes may have a significant impact in CRC patients with poor-risk prognosis worldwide as 40-50% of them present gene expression profiles matching one of the 3 approaches. Around 40,000 European CRC patients may potentially benefit from the results. Also, these may be translated to other cancer types with equivalent gene expression patterns/deregulated signalling pathways. Fields of science medical and health sciencesclinical medicineoncologycolorectal cancernatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicineimmunologyimmunotherapymedical and health scienceshealth sciencespublic healthepidemiologymodeling of diseases spread Programme(s) H2020-EU.3.1. - SOCIETAL CHALLENGES - Health, demographic change and well-being Main Programme H2020-EU.3.1.3. - Treating and managing disease Topic(s) PHC-13-2014 - New therapies for chronic non-communicable diseases Call for proposal H2020-PHC-2014-2015 See other projects for this call Sub call H2020-PHC-2014-two-stage Funding Scheme RIA - Research and Innovation action Coordinator FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON (VHIO) Net EU contribution € 1 049 062,50 Address Calle nazaret 115-117 08035 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Participants (9) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSTITUT CATALA D'ONCOLOGIA Spain Net EU contribution € 683 427,50 Address Av gran via de l'hospitalet 199-203 08908 L'hospitalet del llobregat See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 AGENDIA NV Netherlands Net EU contribution € 905 250,00 Address Radarweg 60 1043 NT Amsterdam See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS Netherlands Net EU contribution € 643 218,75 Address Plesmanlaan 121 1066 CX Amsterdam See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER AISBL Belgium Net EU contribution € 331 000,00 Address Avenue e. mounier 83 1200 Bruxelles / brussel See on map Region Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 L'AZIENDA SOCIO SANITARIA TERRITORIALE (ASST) GRANDE OSPEDALE METROPOLITANO NIGUARDA Italy Net EU contribution € 207 501,25 Address Piazza ospedale maggiore 3 20162 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 FUNDACION PARA LA INVESTIGACION DEL HOSPITAL CLINICO DE LA COMUNITAT VALENCIANA, FUNDACION INCLIVA Spain Net EU contribution € 143 031,50 Address Av menendez pelayo 4 46010 Valencia See on map Region Este Comunitat Valenciana Valencia/València Activity type Research Organisations Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITA DEGLI STUDI DELLA CAMPANIA LUIGI VANVITELLI Italy Net EU contribution € 146 500,50 Address Viale abramo lincoln 5 81100 Caserta See on map Region Sud Campania Caserta Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITA DEGLI STUDI DI TORINO Italy Net EU contribution € 682 125,00 Address Via giuseppe verdi 8 10124 Torino See on map Region Nord-Ovest Piemonte Torino Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 KATHOLIEKE UNIVERSITEIT LEUVEN Belgium Net EU contribution € 157 625,50 Address Oude markt 13 3000 Leuven See on map Region Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00