MoTriColor launches as a pan-European project aimed at the development of novel therapies for patients with advanced colorectal cancer

This week marks the kick-off meeting of the MoTriColor Consortium. Convening some of the most internationally renowned experts in colorectal cancer, project participants have joined together in Barcelona to initiate this inspired project led by the Vall d´Hebron Institute of Oncology (VHIO). Spurred by Horizon 2020 funding, MoTriColor was selected from a highly competitive Call centering on New therapies for chronic non-communicable diseases. MoTriColor will conduct multi-center early phase clinical trials to establish the anti-tumor activity of novel experimental therapies for patients with metastatic or advanced colorectal cancer (CRCm).

Colorectal cancer is as complex as it is heterogeneous. Currently ranking third in the leading causes of death by cancer worldwide, with some 1,400,000 cases per year according to figures reported by the World Health Organization, colorectal cancer too often goes undetected in the early stages of disease, manifesting itself at advanced stages and therefore limiting the therapeutic options available. Furthermore, the classified molecular subtypes of CRC manifest alterations in different signaling pathways and as a consequence, prognosis and response to therapy vary tremendously across these subtypes.

Strategies aimed at patient stratification depending on each individual molecular profile are currently based on tumor mutations. MoTriColor will go one step further – for the first time patients will be stratified based on their gene expression profiles according to recently established predictive signatures. According to gene expression profiles, patients will then be matched to a particular clinical trial.This pioneering approach aims at identifying sensitivity of individual patients to the proposed experimental therapies towards ultimately developing more precise anti-cancer therapies for these patients.

“Given that colorectal cancer generally bears a particularly poor prognosis, and that there are few therapeutic options for these patients, we must strive to develop and validate new therapeutic options targeted and tailored to the particularities of each tumor and each individual patient. We estimate that between 25-30% of colorectal cancer patients with advanced disease, who have not responded to currently available, standard therapies, will present at least one gene expression profile that will permit their inclusion in early phase MoTriColor clinical studies. The sub-classification of tumors is vital since these subtypes show important behavioural differences in terms of the response to therapy”, explains Josep Tabernero, Director of the Vall d´Hebron Institute of Oncology (VHIO), Head of the Medical Oncology Department of Vall d’Hebron University Hospital (HUVH), and Principal Investigator of MoTriColor.

“MoTriColor is based on the promising results previously reported by the Consortium through other collaborative and translational research projects of excellence, such as the previous FP7-funded COLTHERES Colon Therapy Research Consortium. The MoTricolor studies will provide new hope to CRC patients with advanced disease by offering more tailored and precise treatments based on the different subtypes”, he continues.

MoTriColor, a four-year project, will perform phase II studies across Europe for the treatment of molecular subgroups of CRC patients with advanced disease. The primary objectives of these clinical studies are to determine clinical efficacy (progression-free survival as primary endpoint), safety and tolerability of the experimental treatments in these groups of patients. MoTriColor will also create a tumor biorepository - a shared biobank among partners - which will not only accelerate research, facilitate translational studies in parallel, but also represent an invaluable resource for later research. Furthermore, within the framework of the project, novel biomarkers for prediction of treatment response may also be revealed through the mutational analysis of samples prior to treatment as well as during progression via the liquid biopsy ´policing ´ of disease. This in turn could lead to the identification of new predictive signatures. While MoTriColor centers on patients with colorectal cancer, results could also later be applied to other tumor types with equivalent molecular alterations.

Powered by eight clinical research centers of excellence, spanning Spain, Italy, The Netherlands and Belgium, as well as a European organization in cancer research and a diagnostic/prognostic SME, the MoTriColor Consortium* has been carefully devised and structured to incorporate renowned leaders and institutions with the necessary expertise within the field to deliver on the project´s objectives.

Studying response to therapy in ´real time´: from MoTri to Intra-Color

The Consortium has also received complementary EU funding (through TRANSCAN 2015 from the ERA-NED program of H2020), to fuel a second proposal: IntraColor. To run in parallel with MoTriColor, IntraColor will facilitate the collection and analysis of tumor samples at disease initiation and progression to generate cancer ´avatars´ (patient-derived xenograft (PDX) mouse models), for the study of tumor heterogeneity, treatment efficacy, and primary or acquired resistance to MoTriColor´s experimental therapies.

“It is thanks to the IntraColor project that the Consortium will also be able to better track disease status in patients participating in the MoTriColor clinical trials, enabling us to detect possible relapse and study the reasons why”, observes Alex Piris, Head of VHIO´s Scientific Coordination Area, and Scientific Coordinator of MoTriColor and IntraColor.

“MoTriColor represents a tremendous undertaking. Funding received from the European Union to support these two major projects will undoubtedly further establish VHIO as a leading reference in colorectal cancer research from concept to the clinic.” concludes Piris.