DITEP 2018 01 � Gustave Roussy is one of the largest phase 1 centre, with more than 450 patients included per year in phase 1 trials. The mission of the DITEP is to accelerate the development of new anticancer drugs, to build an ambitious cancer research program (precision medicine, immunotherapy and new targets), and also to give a new hope to patients facing cancer battles. � Dr. Christophe Massard Head of DITEP 3 OUR STRATEGIC VISION AND MISSIONS Created on September 1st, 2013 to strengthen the therapeutic innovation and the early clinical trials at Gustave Roussy. In 2018, this medical department carries the ambition to be one of the top international players in early drug development, precision medicine and immunotherapy. OUR STRATEGIC VISION AND MISSIONS Created on September 1st, 2013 to strengthen the therapeutic innovation and the early clinical trials at Gustave Roussy. In 2018, this medical department carries the ambition to be one of the top international players in early drug development, precision medicine and immunotherapy. Oncology has become in the last decade an exciting therapeutic area bridging new scientific concepts and major clinical breakthroughs for the patients and their families. Our ambition is to foster a new era of cancer care and treatments by: Promoting innovation and multidiscipli- Continuously developing the medico- nary collaborations to achieve higher scientific expertise of our investigators rates of treatment efficacy based on team and the skills and performance streamlined molecular analyses and of our clinical operations staff through predictive tools generated from our fruitful collaborations and partnerships precision medicine programs, as well with pharma and biotech companies. as innovative imaging methods. Pursuing our quality assurance Facilitating patients’ inclusion in phase management in the context of ISO- I/II studies at an earlier stage of the 9001 certification. disease to acknowledge the early clinical trial as a true therapeutic opportunity within an integrated cancer care management structure. Positioning cancer immunotherapy and the novel immunomodulators as early as possible as potential backbone therapies for combinations with other approaches. OVERALL ORGANIZATION OF THE DITEP DITEP KEY STEPS September 2006 Early drug development and clinical trials identified as a strategic orientation of Gustave Roussy. Prof Soria appointed as the leader of a working group for therapeutic innovation and early clinical trials expansion. September 2007 Establishment of the early clinical trial pluridisciplinary committee (RCP-150) September 2008 Creation of the « SITEP » (Service des Innovations Thérapeutiques et Essais Précoces), first hospitalization unit in France fully dedicated to early clinical trials in oncology (first-in-human administration, phase I trials, phase October 2010 I/II extension cohorts) with 8 beds and 6 out- patient seats. Recognition granted by the french National Cancer Institute (INCA, 4 years) of SITEP as an early trials center (CLIP²) July 2011 Certification of the french Health Regional Agency (ARS, 5 years) for first-in-human trials September 2013 Creation of the DITEP as a full medical department of Gustave Roussy , headed DITEP Drug Development Department by Prof. Soria. February 2015 Renewal of the CLIP² label by INCA (4 years) May 2015 New premises gathering all the DITEP teams on one floor (4th) September 2016 Renewal of the ARS certification for first-in-human trials November 2016 ISO 9001 accreditation N°2016/72604.1 September 2017 Dr Massard appointed as Head of the DITEP Headed by Dr. Christophe Massard, in 2018 the DITEP encompasses 150 full-time equivalents dedicated to early clinical trials, translational research and precision medicine programs. Since November 2016, the DITEP has obtained the ISO 9001v2015 certification (Quality Management System) for its activities of access to therapeutic innovations, management of early clinical trials, and scientific outreach. MEDICAL AND CLINICAL OPERATION TEAMS • Principal investigators and sub-investigators: 6 MD-PhD, 7 MDs (see CV p.28-40) • Medical and academic assistants & Managers: 13 • Clinical research nurses & Managers: 40 • Head of clinical operation unit: 1 • CRA managers: 2 • Project managers: 7 • Study coordinators: 26 • Clinical research technicians & sample managers: 17 • Schedulers: 3 • Medical research assistants & helpers: 7 • Quality assurance: 1 • Administrative & contracting: 3 • Chief scientific officer: 1 PLURIDISCIPLINARY CLINICAL RESEARCH AND DECISION-MAKING COMMITTEES • The early clinical trial multi-disciplinary tumor board (RCP-150), headed by Dr Vincent Ribrag, encompasses all DITEP experts in medical oncology, radiotherapy, hematology, immunotherapy, as well as experts in biopathology and imaging. This weekly committee is in charge of the validation of all patients’ referral to our phase I programs, and for the review of all on-going trials and medical decisions regarding any complex situations of safety or experimental treatment decisions. • The molecular pluridisciplinary committee (RCPM-150), dedicated to the weekly review of the molecular tumor profiles performed within our precision medicine programs aims at including each phase I-eligible patient in the most adapted clinical trial based on actionable molecular abnormalities. • A monthly Protocol Review Committee (PRC) to address the scientific value and feasibility of new trials proposals. CARE WARDS & FACILITIES • A conventional week-hospitalization unit (4th floor) headed by Dr Antoine Hollebecque: 13 single-patient beds. This unit receives patients who require full-time hospitalization as per protocol or for safety surveillance due to side effects over the week. • An out-patient care unit (4th floor) headed by Dr Andrea Varga: 16 armchairs (whose 2 dedicated to PK). This outpatient unit is operational every day from Monday to Friday from 7:00 am to 7:00 pm (including PK sampling on Saturdays). This unit also receives patients who require nursing and related cares. • A consultation platform facility • An early phase clinical operations unit (4th floor) headed by Mrs Guylène Chartier gathering all staff in the same new premises that host all MDs offices, a local laboratory dedicated to the processing of biological samples, as well as confidential monitoring spaces dedicated to the trials sponsors. 09 ORGANIZATION CHART Head of Department Dr A. Marabelle - Clinical Director of the Cancer Immunotherapy Program functional link Dr E.Angevin - Industrial Partnerships Alliance Manager. Dr. C. Massard Dr J.P.Armand - Senior scientific consultant. Pr E.Deutsch - Head of Radiotherapy Department. Dr V.Ribrag - Head of Early Drug Development multidisciplinary tumor board Dr S. Postel-Vinay - Physician Senior Scientist (UMR 981) functional link Principal Academic functional link External consultant assistant J.Florance B.Thuillier 2 academic assistants Head of early phase Executive Head of medical Head of Head of outpatient Clinical care Clinical care clinical operations unit Assistant secretary hospitalization unit care unit coordinator coordinator QA officer Manager P. Dielenseger G. Bernal- E. Netzer G. Chartier D. Aubry K. Willinger Dr A. Hollebecque Dr A. Varga Trinel 1 Head nurse DITEP 26 study-co 1 principal MA Dr A.Gazzah (day) Dr R.Bahleda 1 Head 2 CRA managers S. Orange Dr J.M.Michot S.Rodrigues nurse 10 data-managers Dr S. Champiat Dr C. Baldini (night) M.Houssaini 5 MA H. Zouhri 5 Sample managers + 25 nurses N. Meunier 2 Medical 1 assistant Administrative KEY FIGURES 1 Contract and Finance manager Secretaries 4 Nurse 7 nurses 1 Finance coordinator + helpers (night) L. Daley 1 Contract coordinator 1 professional training contract 1 Operations 4 Medical clinical Abbreviations coordinator research assistants S. Lancereau + 3 helpers AMR MA : Medical Assistant QA : Quality Assurance 3 schedulers EP : Early Phase 2 project managers CR : Clinical Research in personalized CRA : Clinical Research Associate medecine 2 Data Managers M. Ngo Camus C. Nicotra 1 project manager in Immunotherapy S. Fahrane 5 industrial partnerships project managers F.Colame N. Imam E. Toubiwou E. Zedouard H. Pousse 1 Chief Scientific Officer N. Hainault DITEP KEY FIGURES 2017 KEY FIGURES 3.946stays (Conventional Hospital and Day Hospital) 3.504 medical consultations 34 publications on early clinical trials results and precision medicine programs 11,2as the average journal Impact Factor 2.080 patient’s referrals for inclusion in early clinical trials 104 early clinical trials opened for inclusions 460 patients recruited in early clinical trials 806 patients recruited in precision medicine programs MAIN ACTIVITY INDICATORS Yearly number of ongoing early clinical trials 104 100 96 91 90 88 80 70 70 68 60 55 50 41 40 30 20 10 0 20102011 2012 2013 2014 2015 2016 2017 Early clinical trials, as of January 2018 (in dose escalation and in organ-oriented extension cohorts) 8 3 Other Cell cycle & Apoptosis 6 Epigenetic & metabolic Inhibitors 41 86 Immune Checkpoints 10 & Immunomodulators Antibody Drug Conjugates EARLY CLINICAL & Bispecific Monoclonal TRIALS Antibodies 18 Tyrosine Kinase Inhibitors 13 Patients recruited in DITEP trials 1000 1266 932 900 863 800 757 700 647 600 519 500 460 444 410 443 400 385 344 336 345 300 279 278 200 100 0 2010 2011 2012 2013 2014 2015 2016 2017 Patients recruited in our studies (early clinical trials and precision medicine programs) Patients treated in our early clinical trials (inclusions in our precision medicine programs