The MoTriColor work has been focused in the implantation of the screening program to identify patients with mCRC, the setting up and execution of the three clinical trials (CT1, CT2, and CT3 ) and the associated translational research. Importantly, efforts have been devoted to the dissemination and exploitation of the project results and the overall management of the project.
Regarding the screening program, we have developed three gene expression signatures that read TGFβ activated-like, BRAF mutant-like, and MSI-like profiles on FPPE tumour biopsies and we have established all the procedures and circuits to carry out the screening of patients. During the whole project 954 samples have been registered and 635 have been analysed. A total of 364 have been eligible for at least one of the three MoTriColor trials.
In parallel, the setup of the three clinical trials was concluded putting in place all the logistics and legal aspects to open the three clinical trials in Belgium, Italy, The Netherlands, and Spain. The preparative tasks also included conversations and agreements with two pharmaceutical companies that would provide novel drugs for two of the three trials. In addition, amendments have been performed in the trials protocols in order to adapt them to new safety requirements, the current regulation, and to mitigate unforeseen threats as the COVID-19 outbreak. However, this process took longer than expected due to long protocol negotiation with the pharmaceutical companies, delays in getting the approvals in the different Competent Authorities and Ethics Committees, the change of the Sponsor Principal Investigator for CT1 and CT2.
In addition, CT1 had to deal with discontinuity of the distribution of the CT1 therapy just one month before starting the recruitment: the TGFβ inhibitor. After several conversations with different pharmaceutical companies with TGFβ inhibitors in the pipeline, at the end of RP3 CT1 was not initiated.
On the other hand, CT2 was activated in all centres and, at the end of RP3, it was closed due to futility.
The European Commission granted an exceptional 8-months extension (RP4) to continue only with CT3. This was followed by a new extension of 6-months to deal with the COVID-19 related impacts. CT3 had concluded the recruitment with 46 patients enrolled. These patients had MSI-like tumours as assessed by the MSI-like FFPE signature and 46% were categorized as MSS by current diagnostic standards.
Moreover, the pipeline for the translational research has been performed. These studies will comprise different bioinformatics and biostatistical analyses, immunological studies and the monitoring of patient-specific mutations by NGS-WES of cell free DNA (cfDNA) in liquid biopsies of selected patients. cfDNA and tumour biopsy DNA have been obtained from patients selected based on RECIST and MSS/MSI status to start full genetic analysis and monitoring.
Finally, the dissemination activities have been carried out in accordance with the communication plan.
