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2 0 1 8D I T E P
3
Dr. Christophe MassardHead of DITEP
� 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. �
OUR STRATEGIC VISIONAND 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 VISIONAND 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-nary collaborations to achieve higher rates of treatment efficacy based on streamlined molecular analyses and predictive tools generated from our precision medicine programs, as well as innovative imaging methods.
Facilitating patients’ inclusion in phase I/II studies at an earlier stage of the 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.
Continuously developing the medico-scientific expertise of our investigators team and the skills and performance of our clinical operations staff through fruitful collaborations and partnerships with pharma and biotech companies. Pursuing our quality assurance management in the context of ISO-9001 certification.
OVERALL ORGANIZATIONOF THE DITEP
September 2006
September 2008
October 2010
February 2015
September 2016
September 2017
May 2015
November 2016
September 2007
July 2011
September 2013
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.
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 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)
Renewal of the CLIP² label by INCA (4 years)
Renewal of the ARS certification for first-in-human trials
Dr Massard appointed as Head of the DITEP
New premises gathering all the DITEP teams on one floor (4th)
Establishment of the early clinical trial pluridisciplinary committee (RCP-150)
Certification of the french Health Regional Agency (ARS, 5 years)
for first-in-human trials
Creation of the DITEP as a full medical department of Gustave Roussy , headed by Prof. Soria.
Drug Development DepartmentDITEP
ISO 9001 accreditation N°2016/72604.1
DITEP KEY STEPS
09
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.
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.
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.
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
09
Dr. C. Massard
Head of Department
Head of early phase clinical operations unit
E. Netzer
QA officer
1 Contract and Finance manager
1 Operations coordinator
Dr E.Angevin - Industrial Partnerships Alliance Manager. Dr J.P.Armand - Senior scientific consultant.Pr E.Deutsch - Head of Radiotherapy Department.Dr V.Ribrag - Head of Early Drug Development multidisciplinary tumor boardDr S. Postel-Vinay - Physician Senior Scientist (UMR 981)
functional link
Principal Academic assistantJ.Florance
functional link
Executive Assistant Manager
Head of hospitalization unit
D. Aubry Dr A. Hollebecque
L. Daley
S. Lancereau
Abbreviations
MA : Medical AssistantQA : Quality AssuranceEP : Early PhaseCR : Clinical ResearchCRA : Clinical Research Associate
External consultant
B.Thuillier
Head of outpatient care unit
Dr A. Varga
Dr R.BahledaDr C. Baldini
Clinical care coordinator
1 Head nurse (day)
25 nurses
S.Rodrigues
4 Nurse helpers
Dr A.GazzahDr J.M.MichotDr S. Champiat
P. Dielenseger
7 nurses (night)
1 Head nurse (night)
Head of medical secretary
K. Willinger
Clinical care coordinator
G. Bernal-Trinel
Dr A. Marabelle - Clinical Director of the Cancer Immunotherapy Program
functional link
2 project managers in personalized medecine
1 project manager in Immunotherapy
1 Chief Scientific Officer
4 Medical clinical research assistants + 3 helpers AMR
3 schedulers
2 Data Managers
1 assistant
1 Finance coordinator1 Contract coordinator
26 study-co
10 data-managers
5 Sample managers
M. Ngo CamusC. Nicotra
S. Fahrane
N. Hainault
5 industrial partnerships project managers
F.Colame N. Imam E. Toubiwou E. ZedouardH. Pousse
2 academic assistants
1 principal MAS. Orange
5 MA+2 Medical Administrative Secretaries+1 professional training contract
2 CRA managers
M.HoussainiH. Zouhri N. Meunier
G. Chartier DITEPKEY FIGURES
ORGANIZATION CHART
DITEPKEY FIGURES
806
34
11,2
patients recruited in precision medicine programs
104
460
2.080
early clinical trials opened for inclusions
patient’s referrals for inclusion in early clinical trials
patients recruited in early clinical trials
3.946
3.504
stays (Conventional Hospital and Day Hospital)
medical consultations
publications on early clinical trials results and precision medicine programs
as the average journal Impact Factor
2017 KEY FIGURES
13
96100
20112010 2012 2013 2014 2015
41
55
68 70
8890
80
70
60
50
40
30
20
10
02016 2017
91
104
Early clinical trials, as of January 2018 (in dose escalation and in organ-oriented extension cohorts)
3 Cell cycle & Apoptosis
41Immune Checkpoints& Immunomodulators
18 Tyrosine Kinase Inhibitors
10Antibody Drug Conjugates
& Bispecific Monoclonal Antibodies
6Epigenetic
& metabolic Inhibitors
8Other
86 EARLY CLINICAL
TRIALS
Yearly number of ongoing early clinical trials
MAIN ACTIVITY INDICATORS
Patients recruited in DITEP trials
Patients treated in early clinical trials in 2017
Patients treated in our early clinical trials (inclusions in our precision medicine programs excluded)
Patients recruited in our studies (early clinical trials and precision medicine programs)
1000
900
800
700
600
500
400
300
200
100
02010 2011 2012 2013 2014 2015 2016 2017
279 278
647
385
932
444
863
1266
443
460
757
410
345
519
344 336
Gastrointestinal
Hematology
Gynaeco
Lung
GenitoUrinary
Breast
HNSCC
Skin
Brain
Neuroendocrine
Other
Sarcoma
32%1%1%
2%2%
5%
5%
5%
10%
11% 12%
14%
460 PATIENTS
DITEP RESEARCH ACTIVITES
MTAs Mol. Profiling/Serial Biopsies
Targeted panel WES/RNASeq/ctDNA
EDD in Hematological Malignancies
PRECISION MEDICINE IMMUNOTHERAPY NEW MOLECULAR ENTITIES
FIHs Dose Escalation (All comers)
Dose Extensions (All indications) Basket / Umbrella Trials
Combos with Radiotherapy
Local Immunomodulation Intratumoral Injections
Neoadjuvant Settings / WoO Trials
DES
IGN
S FI
ELD
S O
F IN
TER
EST
DITEP Research
Axis
ICB FIH & combos ADCs - BiTEs
Cancer Vaccines CAR-T cells
DNA repair Epigenetic Metabolism
SPEC
IFIC
EXP
ERTI
SES
ADC : Antibody Drug Conjugate ; BiTE : Bispecific T cell Engager ; EDD : Early Drug Development ; ICB : Immune Checkpoint Blocker ; MTA : Molecular Targeted Agent ; WoO : Window of Opportunity
DITEP RESEARCH AXIS
17
This Gustave Roussy-sponsored biomedical research exploited the extensive molecular and immunological characterization of on-purpose fresh biopsies of metastatic sites in relapsed and refractory phase I-eligible patients in order to orient these patients to the most adapted molecular targeted or immune-based therapy.
In the first part of this program, named MOSCATO-01, over 1011 patients were included between November 2011 and March 2016. Four hundred eleven patients had an “actionable” molecular abnormality (identified on NGS gene panel, CGHa, IHC analyses and more recently WES/RNASeq) and 199 out them have been treated with an ad hoc targeted molecule. The objective of the study was to demonstrate that the progression-free survival of the first line of oriented treatment (PFS2) was significantly superior to the progression-free survival of the last treatment line before inclusion (PFS1). This judgment criterion was fully achieved with a PFS2/PFS1 ratio > 1.3 in 33% (IC95 PFS ratio: 26-39%) of the patients with a disease control rate of 62% and a median overall survival of 11.3 months. With these results, MOSCATO-01 is the first trial demonstrating a clinical benefit in advanced cancer patients by a large-scale molecular screening and precision medicine approach.
The second part of the program, named MOSCATO-02, was launched in March 2016 by Dr. Antoine Hollebecque. It is an extension of the first part and now includes, on top of the molecular profiling, an immune contexture characterization and an evaluation of the mutational load (WES) for the orientation of the patient to immunotherapy.
PUBLICATIONMassard C, et al. High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial. Cancer Discov. 2017 Jun;7(6):586-595.
1168
554patients enrolled in MOSCATO-01
patients enrolled in MOSCATO-02(as of February 2018)
MOSCATO program(“Molecular Screening for Cancer Treatment Optimization”)
PRECISION MEDICINE PROGRAMS
Dr MASSARD
The MATCH-R trial started in 2014 (PI : Prof. Benjamin Besse, Head of the Medical Oncology Department). It is a two-centre prospective trial sponsored by Gustave Roussy which aims at characterizing the evolution of clonal architecture of tumors from patients treated with molecular targeted therapies.
It is designed to collect fresh tumor biopsies at relapse/recurrence in patients treated with molecular targeted agents (either approved or in early clinical trials of the DITEP portfolio of studies). Eligible patients are patients in progressive disease who previously experienced a significant benefit to a targeted molecules (objective response or long-lasting disease stabilization > 6 months) and availability of an
archived initial tumor material.This MATCH-R program also includes several sub-studies :
- The Bégin Hospital and Gustave Roussy have collaborated to establish one focusing on cancer of the prostate (Dr. Yohann Loriot) in patients resistant to enzalutamide and abiraterone.
- The MATCH-R IMMUNO is a prospective study that aims at identifying molecular mechanisms of resistance to immunotherapies in patients with unresectable or metastatic cancers. Eligible patients in this trial are patients eligible for a treatment with an anti-PD-1 or anti-PD-L1 monoclonal antibody, either in monotherapy or in combination.
FRESH TUMOR
biopsy
Max 21 calendar days
pathological control
CGH Array & NGS/WES/RNAseqctDNA
MOLECULAR SCREENING
ACTIONABLETARGET
IMPROVEOUTCOME
RELEVANTTARGETEDTHERAPY
CLINICAL DECISION TREATMENT
MATCH-R program
Precision medecine scheme
PUBLICATIONPlanchard D, et al. EGFR-independent mechanisms of acquired resistance to AZD9291 in EGFR T790M-positive NSCLC patients. Ann Oncol. 2015 Oct;26(10):2073-8.
223patients enrolled
Prof. BESSE
19
PUBLICATIONPlanchard D, et al. EGFR-independent mechanisms of acquired resistance to AZD9291 in EGFR T790M-positive NSCLC patients. Ann Oncol. 2015 Oct;26(10):2073-8.
Jovelet C, et al. Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial. Clin Cancer Res. 2016 Jun 15;22(12):2960-8.
Koeppel F, et al. Whole exome sequencing for determination of tumor mutation load in liquid biopsy from advanced cancer patients. PLoS One. 2017 Nov 21;12(11):e0188174.
The « Liquid Biopsy » Program is based on the detection in the blood of circulating tumor residues, such as circulating tumor cells (CTC), nucleic acids (ctDNA or ctRNA) using specific highly sensitive and specific assays. The general goal of this approach is to monitor, through a repeatable and safe blood sampling, the clonal evolution of tumors at the cellular and molecular levels under the pressure of targeted therapies and to characterize resistance mechanisms. This program is currently deployed across multiple indications, with a focus on lung cancers, for the tracking of already known (in initial tumor biopsies) molecular aberrations (i.e.
mutations, amplifications, translocations) on oncogeneic drivers (EGFR, ALK, MET, FGFR…) and to evidence any new one that could be associated to primary or secondary resistance (e.g. to immune checkpoints blockers or specific tyrosine-kinase inhibitors).
LIQUID BIOPSY program
1221patients enrolled (CTC)
Dr MARABELLE
Recent years have seen the emergence of new immunotherapies finally effective. These new molecules, mainly monoclonal Antibodies (mAbs), present a novel mechanism of action: by blocking co-inhibitory receptors expressed by T cell they unleash their effector functions. The first generation of these immune-targeted mAbs are blocking immune checkpoint receptors such as CTLA4* and PD1 ** and have revolutionized the treatment of melanoma with metastatic response rates and survival exceptionally increased. The PD1/PD-L1 blocking mAbs also give very encouraging results in cancers of the kidney, lung and other advanced cancers are currently being explored. A new generation of treatments against cancer is born!
* CTLA4: cytotoxic T-lymphocyte-associated protein 4** PD1: Programmed cell death protein 1
In 2015, Gustave Roussy launched an institutional program dedicated to immunotherapy: GRIP (Gustave Roussy Immunotherapy Program). This program aims at strengthening translational research on these new treatments, and accelerating the clinical development of immunotherapy, in order to give access to these treatments to the largest number of patients. Initiated by Professor Alexander Eggermont, General Director of Gustave Roussy, the GRIP program is under the clinical direction of Dr. Aurélien Marabelle and under the scientific direction of Professor Laurence Zitvogel.By reactivating the immune system against cancer cells, these immunotherapies may sometimes provoke auto-immune reactions. These reactions are new and necessitate specific management. In addition, some
rare toxic effects are potentially severe and require early detection. As part of the GRIP, Gustave Roussy has implemented a program designed to manage the adverse effects of immunotherapies. This program has 4 components: a network of organ specialist, institutional management guidelines, the REISAMIC pharmacovigilance registry (Registry of Severe Adverse Effects of Immunomodulating Monoclonal Antibodies in Oncology), and dedicated multidisciplinary team (MDT) meetings.
Clinical Research in immunotherapy
A program dedicated to immunotherapy: GRIP
Number of active Immunotherapy Trials/Year
Number of patients treated in Immunotherapy Trials /Year
2 4 7 11 21 38
52
2 3 3 4 8
14
30
65
0
20
40
60
80
100
120
140
2010 2011 2012 2013 2014 2015 2016 2017Phase II/III Phase I/II
28 31
97 134
200 204
419
539
0
100
200
300
400
500
600
2010 2011 2012 2013 2014 2015 2016 2017
Number of active Immunotherapy Trials/Year
Number of patients treated in Immunotherapy Trials /Year
2 4 7 11 21 38
52
2 3 3 4 8
14
30
65
0
20
40
60
80
100
120
140
2010 2011 2012 2013 2014 2015 2016 2017Phase II/III Phase I/II
28 31
97 134
200 204
419
539
0
100
200
300
400
500
600
2010 2011 2012 2013 2014 2015 2016 2017
Number of active Immunotherapy Trials
Number of patients treated in Immunotherapy Trials
IMMUNOTHERAPY
2121
RADIOTHERAPY
Radiotherapy combinations
The link between development of new anticancer drugs and radiation therapy has been part of the activity of DITEP since its creation. Combination of radiotherapy with nanoparticles, therapies targeting DNA repair mechanisms and immunomodulatory agents are under study. A significant portion of this activity is at the interface with the preclinical research activity developed at Gustave Roussy. The combination of radiotherapy with other anticancer agents is therefore part of a comprehensive development strategy.For these studies, academic funding is of special importance notably in the case of combinations of antiviral agents and radiotherapy.
Radiomics
The Radiomics team of the INSERM U1030 unit (led by Prof. Eric Deutsch) has established a very fruitful collaboration with the group of Pr Nikos Paragios (Centrale Supelec INRIA), bringing world-renowned expertise in imaging analysis and artificial intelligence.Medical image processing and analysis (i.e. radiomics) is a promising and rapidly growing discipline. This new approach consists of the analysis of high dimensional data (typically > 1000 features per volume of interest) extracted from standard medical imaging such as CT-scans, PET or MRI. The underlying assumption is that imaging reflects not only the architecture of the tissues, but also their cellular and molecular composition. The end goal of radiomics is to generate imaging biomarkers as decision support tools for clinical practice and to better understand cancer biology. One of the axes of research is the use of radiomics as a predictor of lymphocytic tumor infiltration and thus of the efficacy of immunotherapies.
HEMATOLOGY
With 19 trials open for hematological malignancies, the DITEP has emerged as a key player in hematology drug development. More than 90 patients were enrolled in these trials in 2016 with myeloid and lymphoid diseases. First in man studies targeting epigenetics (IDH2 and EZH2) open new areas for treating patients and now will enter in phase II and III drug development given the high level of activity observed in trials where the DITEP was largely involved.
On the other hand, targeting immune checkpoints proved to be extremely effective in lymphomas such as Hodgkin disease. During the recent years, a dedicated hematology team within the translational research laboratory has been created and offers now the opportunity to add biological cellular collection and a molecular profile of the patient’s tumors. This molecular profile is implemented for patient’s screening. Our aim will be to characterize more precisely the patient’s tumors and more efficiently propose the relevant trial to the patients according to this updated molecular characterization.
Prof. DEUTSCH Dr RIBRAG
SPECIFIC EXPERTISES
DITEP COLLABORATIONS
1 338 national external referrals in 2017 Soft Tissues – Bone
C. Honoré
Thoracic Pathology B. Besse
Gastro-digestive D. Malka
Endocrine Tumours É. Baudin
Dermatology C. Robert
Cervico-facial Pathology I. Breuskin
Urology L. Albigès
Neurology F. Dhermain
Haematology S. De Botton
Breast S. Delaloge
Gynecology P. Pautier
Paediatric Pathology J. Grill
Genetical Oncologist O. Caron
Active file of patients in 2016
EXTERNAL INTERNAL
Gustave Roussy Tumor Boards (RCP)
DITEP Experts & Referents to RCP
R. Bahleda
A. Gazzah
A. Varga
V. Ribrag JM. Michot
A. Marabelle
C. Massard
A. Hollebecque
2 268
2 198
2 818
4 330
4 749
4 198
4 204
826
3 550
10 651
3 351
2 448
972
Organ-oriented expertise with all other tumor boards and medical departments for the patient referral and facilitation of the transition between early and late phase clinical trials. Most of the DITEP physicians are also organ-specialists partially affiliated to different organ-oriented tumor boards. The radiotherapy (Pr Deutsch, Dr Levy) department is strongly connected to DITEP and the surgery departments participate according to specific needs, especially with the HNSCC Tumor Board (Dr Temam).
Strong links with other French Early Drug Development Centers (CLIP² centers) and networks of international centers in Europe (VHIO, NKI, Cambridge, DKFZ, KI within the Cancer Core Europe consortium headed by Pr Eggermont and Pr Calvo).
RELATIONSHIP WITH INTERNAL (RCP) AND EXTERNAL ONCOLOGISTS
25
Early Drug Development @ DITEP
MECHANISMS OF RESISTANCE
L. Friboulet B. Besse
C. Massard
UMR981
IMMUNOLOGY & IMMUNO-
MONITORING
L. Zitvogel A. Marabelle
N. Chaput
UMR1015 LRTI
BIOPATHOLOGY & BIOLOGICAL
RESOURCES
JY. Scoazec
CRB Biopat.
DNA REPAIR EPIGENETIC
S. Postel-Vinay
BIOINFORMATICS
D. Gautheret L. Verlingue
Dir. Prof. E. Deutsch
MOLECULAR RADIOTHERAPY
E. Deutsch
UMR1030
CLINICAL RESEARCH
TRANSLATIONAL RESEARCH
BASIC RESEARCH
BioInfo Pt LIO ATIP-Avenir HCP
Strong interactions with the Clinical Research Division (DRC), headed by Pr Vassal for the initiation and conduct of Gustave Roussy-sponsored early clinical trials & Investigator-initiated Studies (ISS). The DRC encompasses different entities: the SPEC, headed by Ms Vuillier, in charge of the regulatory affairs and monitoring of investigation sites; the SBE, headed by Dr Benhamou, in charge of early clinical trial biostatistics design (Dr Lanoy, Dr Paoletti), medically-driven data management and analyses of ISS; the UFPV headed by Dr Laghouati, is in charge of the pharmacovigilance declarations and of immune-related SAE, a specific registry (REISAMIC) of immune-checkpoint treatments.
Active contribution in early clinical trials of multiple experts: Biopathology/CRB and Translational Research Platforms (Pr Scoazec) including high-throughput molecular profiling (Dr Lacroix), IHC (Dr Adam), circulating cells (Dr Farace), immunomonitoring (Pr Chaput-Gras), bioinformatics (Mr Meurice); Functional Imaging (Dr Balleyguier, Dr Ammary, Dr Lassau); Nuclear Medicine (Dr Dercle) with a specific innovative program of PET-MRI; Interventional Radiology (Pr De Baere) for sequential biopsies in precision medicine programs; Pharmacology & pharmacokinetics (Dr Paci).
RELATIONSHIP WITH PLATFORMS & RESEARCH TEAMS
The development of collaborations and partnerships with industry are a major objective for Gustave Roussy, and espe-cially DITEP. This objective is supported by an active policy of attracting global phar-maceutical and biotechnology companies.
It is based on the value of our medical and scientific expertise, our operational skills and our clinical and biological resources.
Through industry partnerships, our priority is to have access to the most innovative and potentially effective agents for our patients early in their development.
Our teams are able to propose ancillary projects to optimize development of these molecules, establish the mechanism of their action or define predictive biomarkers
of their effectiveness. This is also the opportunity to collaborate on preclinical and translational studies in biology or ima-ging, connecting academic and industrial researchers and clinicians, thus genera-ting significant benefits in terms of patents and know-how.
Finally, these collaborations are accompa-nied by significant funding to retain skilled personnel and develop new methods.
To this end, DITEP promotes privileged partnerships with pharmaceutical compa-nies likely to give us a substantial portfolio of molecules and early trials.
Contact: Dr Angevin, Alliance [email protected]
CV OF DITEPPRINCIPAL
INVESTIGATORS & SUB-INVESTIGATORS
INDUSTRIAL PARTNERSHIPS
Dr ANGEVIN
CV OF DITEPPRINCIPAL
INVESTIGATORS & SUB-INVESTIGATORS
Christophe Massard
General backgroundChristophe Massard (MD, PhD) medical oncologist, is Chair of Drug Development Department (DITEP), Gustave Roussy, Villejuif, France. He is Consultant Medical Oncologist and full time cancer specialist at Gustave Roussy, half time at Drug Development department (DDD) and joined the faculty in 2006. He is primarily involved in translational cancer research and the design and conduct of early-phase biomarker-driven clinical trials, with a special interest in Genito urinary cancer and Central Nervous System tumor.
Dr Massard received his medical degree from PARIS XI University in 2006, and he got a MSc and PhD from PARIS XI University in 2013. He completed his residency training in Paris Hospital, followed by his fellowship in medical oncology at Gustave Roussy. He is board-certified in Medical Oncology. He did a post-doctoral fellowship in Prof DeBono’s lab at the Royal Marsden Hospital of London and Institute of Cancer Research (London).
Dr Massard is member of ESMO, ASCO, AACR. Over the last 5 years, he was the principal investigators of 15 phase I trials, 1 phase II trial (prostate cancer), and sub-investigator of more than 80 clinical trials (phase 1 trials and GU cancers). He is also involved in translational research aspects related to precision medicine(MOSCATO, MATCH R and PETRUS program). Dr Massard has contributed to over 180 peer-reviewed publications, including publications in European Urology, Annals of Oncology and Journal of Clinical Oncology. . He is also a member of the editorial boards of Bulletin du Cancer, Investigational New Drugs, and European Journal of Cancer.
Research axes: early clinical trials, precision medicine, GU cancers (prostate cancer, bladder cancer and testis), glioma, and circulating biomarkers.
EARLY CLINICAL TRIALS EXPERTISE
ORAL PRESENTATIONS
EORTC-NCI-AACR 2016• First-in-human study of LY3039478, an
oral Notch signaling inhibitor in advanced or metastatic cancer
ASCO 2016• Safety and efficacy of durvalumab (MEDI4736), a
PD-L1 antibody, in urothelial bladder cancer
TAT 2016• Dose escalation study of ODM-203, a selective
dual FGFR/VEGFR inhibitor, in patients with advanced solid tumours
PUBLICATIONS
• Massard C, Mateo J, Loriot Y, Pezaro C, Albiges L, Mehra N, Varga A, Bianchini D, Ryan CJ,
Petrylak DP, Attard G, Shen L, Fizazi K, de Bono J. Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant
prostate cancer (mCRPC) progressing after docetaxel and abiraterone. Ann Oncol.2017 Jan
1;28(1):90-95.
• Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, Curiel TJ, Colon-Otero G, Hamid O, Sanborn RE, O’Donnell PH, Drakaki
A, Tan W, Kurland JF, Rebelatto MC, Jin X, Blake-Haskins JA, Gupta A, Segal NH. Safety
and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced
Urothelial Bladder Cancer. J Clin Oncol. 2016;34(26):3119-25.
• Massard C, Michiels S, Ferte C, Le Deley MC, Lacroix L, Hollebecque A, Verlingue L, Ileana E, Rosellini S, Ammari S, Ngo-Camus M, Bahleda
R, Gazzah A, Varga A, Postel-Vinay S, Loriot Y, Even C, Breuskin I, Auger N, Job B, De Baere
T, Deschamps F, Vielh P, Scoazec JY, Lazar V, Richon C, Ribrag V, Deutsch E, Angevin E,
Vassal G, Eggermont A, Andre F, Soria JC. High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results
of the MOSCATO 01 Trial. Cancer Discov. 2017 Jun;7(6):586-595.
• Massard C, Borget I, Farace F, Aspeslagh S, Le Deley MC, Le Tourneau C, Bidard FC, Pierga JY, Dieras V, Hofman P, Spano JP, Ferte C, Lacroix
L, Soria JC. RECIST response and variation of circulating tumour cells in phase 1 trials: A
prospective multicentric study. Eur J Cancer. 2017;83:185-193.
• Massard C, Chi KN, Castellano D, de Bono J, Gravis G, Dirix L, Machiels JP, Mita A, Gonzalez BM, Turri S, Maier J, Csonka D, Chakravartty A,
Fizazi K (2017) Phase Ib dose-finding study of abiraterone acetate plus buparlisib (BKM120) or
dactolisib (BEZ235) in patients with castration-resistant prostate cancer. Eur J Cancer 76:36-44.
MDPhD
29
General backgroundEric Deutsch, MD, PhD, full-Professor in Radiation Oncology at South-Paris University, head of the Inserm Unit 1030 « Molecular Radiology Laboratory » and Head of the Radiation Oncology Department in Villejuif, France. He is teaching radiobiology and medical physics at the Medical School of South-Paris University.
Eric Deutsch’s research has been dedicated to combination of novel anticancer drugs either used alone or in combination to radiotherapy. His interest focuses on cell death mecanisms, HPV related tumours and the tumour-stroma interplay, on the clinical side, he is versed into the field of translational research and early clinical trials. He has investigated several first in human novel drugs-radiotherapy combinations such as mTOR inhibitors, antiviral agents, immune modifyers and nanoparticles.
Research axes: Early clinical trials and phase I, novel anticancer drugs, radiation biology, HPVs related tumors, combination with new drugs and Radiotherapy.
EARLY CLINICAL TRIALS EXPERTISE
ORAL PRESENTATIONS
NCI-EORTC-AACR 2014• Phase I trial evaluating the antiviral agent CIDOFOVIR in combination whit chemoradiation in cervical cancer patients : a novel approach to treat HPV related malignancies ?
ESMO 2014• Desing of clinical trials integrating local treatments with systemic therapy for M1 disease.
ICTR PHE 2014• Combination of vascular disrupting agents and ionizing radiation.
PUBLICATIONS
• Bonvalot S, Le Pechoux C, De Baere T, Kantor G, Buy X, Stoeckle E, Terrier P, Sargos P, Coindre JM, Lassau N, Ait Sarkouh R, Dimitriu M, Borghi E, Levy L, Deutsch E, Soria JC. First-in-Human Study Testing a New Radioenhancer Using Nanoparticles (NBTXR3) Activated by Radiation Therapy in Patients with Locally Advanced Soft Tissue Sarcomas. Clin Cancer Res 2017. 23:908-917.
• Deutsch E, Cohen-Jonathan Moyal E, Gregorc V, Zucali PA, Menard J, Soria JC, Kloos I, Hsu J, Luan Y, Liu E, Vezan R, Graef T, Rivera S. A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors. Oncotarget. 2016 Dec 24 [Epub ahead of print]
• Levy A, Massard C, Soria JC, Deutsch E. Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Eur J Cancer. 2016;68:156-162.
• Deutsch E, Haie-Meder C, Bayar MA, Mondini M, Laporte M, Mazeron R, Adam J, Varga A, Vassal G, Magne N, Chargari C, Lanoy E, Pautier P, Levy A, Soria JC. Phase I trial evaluating the antiviral agent Cidofovir in combination with chemoradiation in cervical cancer patients. Oncotarget. 2016;7(18):25549-57.
• Deutsch E, Le Péchoux C, Faivre L, Rivera S, Tao Y, Pignon JP, Angokai M, Bahleda R, Deandreis D, Angevin E, Hennequin C, Besse B, Levy A, Soria JC. Phase I trial of everolimus in combination with thoracic radiotherapy in non-small-cell lung cancer. Ann Oncol. 2015;26(6):1223-9.
Eric Deutsch
MDPhD
General backgroundVincent Ribrag attended the University of Science and Medical School of South-Paris University between 1978 and 1985. In 1990-1991 he obtained his Master of Science in Molecular Biology, with Professor JC Kaplan. In the years 1990-1992 he also received his Diplôme d’Études Approfondies in molecular and cellular pharmacology at the Pierre et Marie Curie (Paris Vl) University with Professor Ascher. He obtained his board certification in Hematology and discussed a thesis (silver medal) at the Paris Xl Faculty of Medicine entitled “VIP (etoposide,ifosfamide, cisplatinum) as a salvage intensification program in relapsed or refractory Hodgkin’s disease.”
Dr Ribrag is a tenure-track specialist at Gustave-Roussy lnstitute and has been nominated head of the Hematology multidisciplinary committee in Gustave-Roussy. Among numerous experimental activities, he counts a Laboratoire in clinical pharmacology (URA 147 CNRS, U-140 INSERM) with Dr A Gouyette; works in enzymology , the ICGM: INSERM U-363 at the Hôpital Cochin in Paris; the Unité INSERM U U1170: Animal MCL models and drug discovery and is head of the translational research lab in hematology. Dr Ribrag is member of several international cancer societies, namely the American Association for Cancer Research (AACR), the American Society of Hematology (ASH), the Société Française de Greffe de Moelle (SFGM), the Société Française d’Hématologie (SFH), the Groupe Français des Myélodysplasies (GFM) where he serves as scientific secretary since 1998. He is also part of the Lysa Scientific and Administrative Committees and of the European Scientific Committee of the Mantle Cell Lymphoma study group since 2001 and associated Head of early trials with Martin Dreyling.
EARLY CLINICAL TRIALS EXPERTISE
ORAL PRESENTATIONS
ASH 2015• Phase 1 Study of Tazemetostat (EPZ-6438), an
Inhibitor of Enhancer of Zeste-Homolog 2 (EZH2): Preliminary Safety and Activity in Relapsed or
Refractory Non-Hodgkin Lymphoma (NHL) Patients.
• Safety and Efficacy of Abexinostat, a Pan-Histone Deacetylase (HDAC) Inhibitor, in Non-Hodgkin Lymphoma and Chronic Lymphocytic
Leukemia: Results of an Ongoing Phase 2 Study.
TAT 2015• Phase 1 first-in-human study of the enhancer
of zeste-homolog 2 (EZH2) histone methyl transferase inhibitor E7438.
PUBLICATIONS
• Zinzani PL, Ribrag V, Moskowitz CH, Michot JM, Kuruvilla J, Balakumaran A, Zhang Y, Chlosta
S, Shipp MA, Armand P. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell
lymphoma. Blood. 2017 Jul 20;130(3):267-270.
• Ribrag V, Kim WS, Bouabdallah R, Lim ST, Coiffier B, Illes A, Lemieux B, Dyer MJS,
Offner F, Felloussi Z, Kloos I, Luan Y, Vezan R, Graef T, Morschhauser F. Safety and efficacy
of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic
lymphocytic leukemia: results of a phase II study. Haematologica. 2017 May;102(5):903-909.
• Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C,
Ghesquieres H, Morschhauser F, Girault S, Le Gouill S, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C,
Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for
adults with Burkitt’s lymphoma: a randomised, controlled, open-label, phase 3 trial. 2016 Nov
1;34(31):3733-3739.
• Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, Snyder ES, Ricart AD, Balakumaran A, Rose S, Moskowitz
CH. Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical
Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016 Jun 27. pii: JCO673467
[Epub ahead of print]
• Infante JR, Cassier PA, Gerecitano JF, Witteveen PO, Chugh R, Ribrag V, Chakraborty A, Matano A, Dobson JR, Crystal AS, Parasuraman S, Shapiro
GI. A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients
With Advanced Solid Tumors and Lymphomas. Clin Cancer Res. 2016;22(23):5696-5705.
Vincent Ribrag
MD
31
General backgroundAurélien Marabelle MD, PhD, is a Senior Medical Oncologist in the Drug Development Department (DITEP), a group leader in Prof Laurence Zitvogel’s lab (INSERM U1015) and the Clinical Director of the Cancer Immunotherapy Program at Gustave Roussy. He joined the faculty in Oct 2014.
He got a MSc & PhD in Oncology & Immunology from Ecole Normale Supérieure de Lyon, King’s College London & University of Lyon. He did a post-doctoral fellowship in Prof Ronald Levy’s lab at Stanford University, California.
He trained at the University of Paris VI medical school and received his medical degree from the University of Clermont-Ferrand. He completed his residency training in between Clermont-Ferrand & Lyon, followed by a clinical fellowship at Léon Bérard Cancer Center in Lyon.
Dr Marabelle is a member of ASCO & AACR. Dr Marabelle is board-certified in Pediatric Oncology & Cell Therapy.
Research axes: Cancer Immunotherapy & Early Phase Studies
IMMUNOTHERAPY & EARLY CLINICAL TRIALS EXPERTISE
ORAL PRESENTATIONS
SITC 2017• Phase I study of E7046, a novel PGE2-receptor type-4 inhibitor, in patients with advanced solid tumors: clinical results and effects on myeloid- and T-lymphoid cell-mediated immunosuppression
ASCO GI 2016• Understanding the relevant immune mechanisms in GI cancer
ITOC3 2016• Prioritisation of potential immunotherapy combination studies
TAT 2015• “Novel Immunostimulatory Antibodies: What’s next?”
PUBLICATIONS
• Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, Chaput N, Eggermont A, Marabelle A, Soria JC, Ferte C. Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1. Clin Cancer Res 2017 Apr 15;23(8):1920-1928.
• Marabelle A, Aspeslagh S, Postel-Vinay S, Soria JC. JAK Mutations as Escape Mechanisms to Anti-PD-1 Therapy. Cancer Discov. 2017;7(2):128-130.
• Aspeslagh S, Postel-Vinay S, Rusakiewicz S, Soria JC, Zitvogel L, Marabelle A. Rationale for anti-OX40 cancer immunotherapy. Eur J Cancer. 2016;52:50-66.
• Boutros C, Tarhini A, Routier E, Lambotte O, Ladurie FL, Carbonnel F, Izzeddine H, Marabelle A, Champiat S, Berdelou A, Lanoy E, Texier M, Libenciuc C, Eggermont AM, Soria JC, Mateus C, Robert C. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nature reviews Clinical oncology. 2016;13(8):473-486.
• Postel-Vinay S, Aspeslagh S, Lanoy E, Robert C, Soria JC, Marabelle A. Challenges of phase 1 clinical trials evaluating immune checkpoint-targeted antibodies. Ann Oncol. 2016;27(2):214-224.
• Jacquelot N, Roberti MP, Enot DP, Rusakiewicz S, Ternes N, Jegou S, Woods DM, Sodre AL, Hansen M, Meirow Y, Sade-Feldman M, Burra A, Kwek SS, Flament C, Messaoudene M, Duong CPM, Chen L, Kwon BS, Anderson AC, Kuchroo VK, Weide B, Aubin F, Borg C, Dalle S, Beatrix O, Ayyoub M, Balme B, Tomasic G, Di Giacomo AM, Maio M, Schadendorf D, Melero I, Dreno B, Khammari A, Dummer R, Levesque M, Koguchi Y, Fong L, Lotem M, Baniyash M, Schmidt H, Svane IM, Kroemer G, Marabelle A, Michiels S, Cavalcanti A, Smyth MJ, Weber JS, Eggermont AM, Zitvogel L. Predictors of responses to immune checkpoint blockade in advanced melanoma. Nat Commun. 2017 Sep 19;8(1):592.
• Shekarian T, Valsesia-Wittmann S, Brody J, Michallet MC, Depil S, Caux C, Marabelle A. Pattern recognition receptors: immune targets to enhance cancer immunotherapy. Ann Oncol. 2017 Aug 1;28(8):1756-1766.
Aurélien Marabelle
MDPhD
General backgroundEric Angevin obtained his medical and biology degree at Paris VI University and a PhD degree of cancerology and tumor immunology at South Paris XI University, while being appointed at Gustave Roussy as medical oncologist in 1995 in the Immunotherapy and Novel Therapies unit of the Medical Oncology Department.
In 2006, he was appointed Assistant Director of Clinical Research in charge of innovation and valorisation, and joins the newly created Early Clinical Trial/phase I Department (DITEP). He has been involved as principal or sub-investigator of more than 200 clinical trials during the last 15 years, including FIH phase I studies across all tumor types. With a specific expertise in immunotherapy and targeted molecules, both at the clinical and translational research levels, he published more than 100 papers in international peer-reviewed journals.
As GR Alliance Manager, he is also in charge of the industrial partnering and collaboration initiatives with pharma/biotech companies at the institutional level. He has been invited to several advisory boards and is an active member of the French Cancer Institute Early Clinical Trials working group (INCA-CLIP²) and of ASCO, AACR, ESMO, EORTC-NCI-AACR and TAT international meetings.
EARLY CLINICAL TRIALS EXPERTISE
ORAL PRESENTATIONS
IASLC WCLC 2016• First-In-Human Phase 1 Study of ABBV-399, an Antibody-Drug Conjugate (ADC) Targeting C-Met,
in Patients with Non-Small Cell Lung Cancer (NSCLC)
ASCO 2015• First-in-human phase I administration of YS110, a monoclonal antibody directed against the CD26 immunostimulatory molecule in advanced cancer
patients (Poster Discussion)
ASCO 2014 • A first-in-human (FIH) phase I study of
SAR125844, a novel selective MET kinase inhibitor, in patients (pts) with advanced solid tumors
PUBLICATIONS
• Angevin E, Spitaleri G, Rodon J, Dotti K, Isambert N, Salvagni S, Moreno V, Assadourian S,
Gomez C, Harnois M, Hollebecque A, Azaro A, Hervieu A, Rihawi K, De Marinis F. A first-in-
human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with
advanced solid tumours with MET amplification.Eur J Cancer. 2017 Dec;87:131-139.
• Angevin E, Cassier PA, Italiano A, Gonçalves A, Gazzah A, Terret C, Toulmonde M, Gravis G, Varga A, Parlavecchio C, Paci A, Poinsignon V, Soria J-C,
Drubay D, Hollebecque A. Safety, tolerability and antitumour activity of LY2780301 (p70S6K/AKT
inhibitor) in combination with gemcitabine in molecularly selected patients with advanced or metastatic cancer: a phase IB dose escalation
study. Eur J Cancer. 2017;83:194-202.
• Angevin E, Isambert N, Trillet-Lenoir V, You B, Alexandre J, Zalcman G, Vielh P, Farace F, Valleix F, Podoll T, Kuramochi Y, Miyashita I, Hosono O,
Dang NH, Ohnuma K, Yamada T, Kaneko Y, Morimoto C. First-in-Human phase 1 of YS110, a
monoclonal antibody directed against CD26 in advanced CD26-expressing cancers. Br J Cancer.
2017 Apr 25;116(9):1126-1134.
• Angevin E, Tabernero J, Elez E, Cohen SJ, Bahleda R, van Laethem JL, Ottensmeier C,
Lopez-Martin JA, Clive S, Joly F, Ray-Coquard I, Dirix L, Machiels JP, Steven N, Reddy M, Hall B,
Puchalski TA, Bandekar R, van de Velde H, Tromp B, Vermeulen J, Kurzrock R. A phase I/II, multiple-dose, dose-escalation study of
siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors.
Clin Cancer Res. 2014;20:2192-2204.
• Angevin E, Lopez-Martin JA, Lin CC, Gschwend JE, Harzstark A, Castellano D, Soria JC, Sen P,
Chang J, Shi M, Kay A, Escudier B. Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and
PDGFR inhibitor, in advanced or metastatic renal cell carcinoma. Clin Cancer Res. 2013 Mar
1;19(5):1257-68.
Eric Angevin
MDPhD
33
General backgroundAntoine Hollebecque (M.D.) is a senior medical physician at Gustave Roussy Cancer Center in Paris. He received his medical degree from Lille2 University in 2008. He completed his residency training followed by his fellowship in hepato-gastroenterology at Lille2 University.
He spent 2 years as an Assistant Professor in the Drug Development Department at Gustave Roussy Cancer Center in 2012-2013. He completed his training with a one-year post-doctoral fellowship in the Clinical and Experimental Pharmacology (CEP) (Pr C. Dive), Manchester Institute, Cancer Research UK, Manchester where he worked on cell-free DNA. Over the last 5 years, Dr Hollebecque was the principal investigator of 20 phase I trials and sub-investigator of more than 100 phase I. He has contributed to over 64 peer-reviewed publications, including publications in New England Journal of Medicine, Journal of Clinical Oncology, European Journal of Cancer, Gastroenterology, Hepatology. Dr Hollebecque is a member of the European Society of Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR).
Research axes: early phase studies, gastro-intestinal cancers, cell-free DNA, Next Generation Sequencing.
EARLY CLINICAL TRIALS EXPERTISE
ORAL PRESENTATIONS
ASCO 2017• An Open-Label, Multicohort, Phase 1/2 Study of Nivolumab in Patients With Virus-Associated Tumors (CheckMate 358): Efficacy and Safety in Recurrent or Metastatic (R/M) Cervical, Vaginal, and Vulvar Cancers.
ASCO 2013• Molecular screening for cancer treatment optimization (MOSCATO 01): A prospective molecular triage trial-Interim results
TAT 2012• A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with erlotinib or everolimus in patients with solid tumours
PUBLICATIONS
• Tacher V, Le Deley MC, Hollebecque A, Deschamps F, Vielh P, Hakime A, Ileana E, Abedi-Ardekani B, Charpy C, Massard C, Rosellini S, Gajda D, Celebic A, Ferte C, Ngo-Camus M, Gouissem S, Koubi-Pick V, Andre F, Vassal G, Deandreis D, Lacroix L, Soria JC, De Baere T. Factors associated with success of image-guided tumour biopsies: Results from a prospective molecular triage study (MOSCATO-01). Eur J Cancer. 2016;59:79-89.
• Jovelet C, Ileana E, Le Deley M-C, Motte N, Rosellini S, Romero A, Lefebvre C, Pedrero M, Pata-Merci N, Droin N, Deloger M, Massard C, Hollebecque A, Ferte C, Boichard A, Postel-Vinay S, Ngo-Camus M, De Baere T, Vielh P, Scoazec J-Y, Vassal G, Eggermont AM, Andre F, Soria J-C, Lacroix L. Circulating cell-free tumor DNA (cfDNA) analysis of 50-genes by next-generation sequencing (NGS) in the prospective MOSCATO trial. Clin Cancer Res. 2016;22(12):2960-8.
• Isambert N, Delord JP, Soria JC, Hollebecque A, Gomez-Roca C, Purcea D, Rouits E, Belli R, Fumoleau P. Debio0932, a second-generation oral heat shock protein (HSP) inhibitor, in patients with advanced cancer-results of a first-in-man dose-escalation study with a fixeddose extension phase. Ann Oncol. 2015;26(5):1005-1011.
• Infante JR, Hollebecque A, Postel-Vinay S, Bauer TM, Blackwood E, Evangelista M, Mahrus S, Peale F, Lu X, Sahasranaman S, Zhu R, Chen Y, Ding X, Murray E, Schutzman J, Lauchle JO, Soria JC, LoRusso PM. Phase I Study of GDC-0425, a checkpoint kinase 1 inhibitor, in combination with gemcitabine in patients with refractory solid tumors. Clin Cancer Res. 2017 May 15;23(10):2423-2432
• Temam S, Spicer J, Farzaneh F, Soria JC, Oppenheim D, McGurk M, Hollebecque A, Sarini J, Hussain K, Soehrman Brossard S, Manenti L, Evers S, Delmar P, Di Scala L, Mancao C, Feuerhake F, Andries L, Ott MG, Passioukov A, Delord JP. An exploratory, open-label, randomized, multicenter study to investigate the pharmacodynamics of a glycoengineered antibody (imgatuzumab) and cetuximab in patients with operable head and neck squamous cell carcinoma. Ann Oncol. 2017 Nov 1;28(11):2827-2835.
• Hollebecque A, Bahleda R, Faivre L, Adam J, Poinsignon V, Paci A, Gomez-Roca C, Thery JC, Le Deley MC, Varga A, Gazzah A, Ileana E, Gharib M, Angevin E, Malekzadeh K, Massard C, Soria JC, Spano JP. Phase I study of temsirolimus in combination with cetuximab in patients with advanced solid tumours. Eur J Cancer 2017:81:81-89.
Antoine Hollebecque
MD
General backgroundAndreea Varga, MD, Senior Medical Oncologist in the Drug Development Department of Gustave Roussy Cancer Campus since 2011. She received her medical degree from Medical Faculty Cluj-Napoca Rumania in 2004.
She started her training in Medical Oncology at Cluj-Napoca University (2005-2010) in oncology, cardiology, internal medecine and radiology units ,then at Paul Brousse Hospital in Paris (2008-2009) and breast cancer unit of Institut Gustave Roussy (2009-2010).
She continued her clinical research residency at IGR (2009-2010) and became medical oncologist of phase I Unit (Pr Soria) in 2011. In september 2017, she was appointed Head of the DITEP out-patient day care unit. Dr Varga is board-certified in Medical Oncology since 2010.
Research axes: phase I trials, drug development, targeted and personalized therapy of breast cancer, lung and other solid tumors.
EARLY CLINICAL TRIALS EXPERTISE
ORAL & POSTER PRESENTATIONS
EORTC-NCI-AACR 2016• A first-in-human phase I study to
evaluate the ERK1/2 inhibitor GDC-0994 in patients with advanced solid tumors
ASCO 2015• Antitumor activity and safety of
pembrolizumab in patients with PD-L1 positive advanced ovarian cancer: Interim
results from a phase Ib study
ECC 2015• Activity of rociletinib in EGFR mutant NSCLC patients with a history of CNS
involvement
PUBLICATIONS
•Massard C, Mateo J, Loriot Y, Pezaro C, Albiges L, Mehra N, Varga A, Bianchini
D, Ryan CJ, Petrylak DP, Attard G, Shen L, Fizazi K, de Bono J. Phase I/II trial of cabazitaxel plus abiraterone in patients
with metastatic castration-resistant prostate cancer (mCRPC) progressing
after docetaxel and abiraterone. Ann Oncol. 2016 Oct 18. pii: mdw441 [Epub
ahead of print]
• Jung J, Lee JS, Dickson MA, Schwartz GK, Le Cesne A, Varga A, Bahleda
R, Wagner AJ, Choy E, de Jonge MJ, Light M, Rowley S, Mace S, Watters J.
TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-
differentiated liposarcoma. Nat Commun. 2016;7:12609.
• Morschhauser F, Terriou L, Coiffier B, Bachy E, Varga A, Kloos I, Lelievre H,
Sarry AL, Depil S, Ribrag V. Phase 1 study of the oral histone deacetylase inhibitor
abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or
chronic lymphocytic leukaemia. Invest New Drugs. 2015;33 (2):423-431.
• Bahleda R, Sessa C, Del Conte G, Gianni L, Capri G, Varga A, Oprea C,
Daglish B, Hospitel M, Soria JC. Phase I clinical and pharmacokinetic study of ombrabulin (AVE8062) combined
with cisplatin/docetaxel or carboplatin/ paclitaxel in patients with advanced
solid tumors. Invest New Drugs. 2014; 32(6):1188-96.
• Frenel JS, Le Tourneau C, O’Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, van
Brummelen EMJ, Rugo HS, Thomas S, Saraf S, Rangwala R, Varga A . Safety and
Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive
Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial. J Clin Oncol. 2017
Dec 20;35(36):4035-4041.
Andrea Varga
MD
35
General backgroundRastislav Bahleda, MD, Senior Medical Oncologist in the Drug Development Department of Gustave Roussy Cancer Campus since 2007. He received his medical degree from Medical Faculty of Comenius University in Bratislava (1995) and completed his clinical residency in Internal Medicine (1998).
He continued his training to complete a fellowship in Clinical Oncology at Comenius University and National Cancer Institut in Bratislava (1995-2001). He continued clinical and molecular research (Inserm U 268) in sarcomas at Institut Gustave Roussy (2002-2003) and received University Diploma in Clinical Research from University of Paris XI.
He continued his clinical research residency at IGR (2003-2006) and became medical oncologist at the Medical Oncology Department (2007), and the Drug Development Department (2013).
Dr Bahleda is board-certified in Internal Medicine and Medical Oncology and a member of ASCO.
Research axes: phase I trials, drug development, oncogenic mutations, FGFR pathway, personnalized and molecular targeted therapy.
EARLY CLINICAL TRIALS EXPERTISE
ORAL PRESENTATIONS
ESMO 2017• Long-Term Safety and Clinical Outcomes of Atezolizumab in Head and Neck Cancer: Phase Ia Trial Results
ASCO 2014• Phase 1 study of JNJ-42756493, a pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients with advanced solid tumors (oral)
PUBLICATIONS
• Bahleda R, Varga A, Berge Y, Soria JC, Schnell D, Tschoepe I, Uttenreuther-Fischer M, Delord JP. Phase I open-label study of afatinib plus vinorelbine in patients with solid tumours overexpressing EGFR and/or HER2. Br J Cancer. 2018 Feb 6;118(3):344-352.
• Bahleda R, Baker J, Massard C, Gadgeel SM, Rogers JE, Izzedine H, Deutsch E, Garris JL, Khan A, Boelle E, Assadourian S, Soria JC, Ajani JA. Phase I Dose-Escalation and Pharmacokinetic Study of Intravenous Aflibercept in Combination with Docetaxel, Cisplatin, and 5-Fluorouracil in Patients with Advanced Solid Malignancies. Oncology. 2016;90(1):10-20.
• Awada A, Campone M, Varga A, Aftimos P, Frenel J-S, Bahleda R, Gombos A, Bourbouloux E, Soria J-C. An open-label, dose-escalation study to evaluate the safety and pharmacokinetics of CEP-9722 (a PARP-1 and PARP-2 inhibitor) in combination with gemcitabine and cisplatin in patients with advanced solid tumors. Anti-Cancer Drugs. 2016;27(4):342-8.
• Calvo E, Soria JC, Ma WW, Wang T, Bahleda R, Tolcher A, Gernhardt D, O’Connell J, Millham R, Giri N, Wick MJ, Adjei AA, Hidalgo M. A Phase I Clinical Trial and Independent Patient-derived Xenograft Study of Combined Targeted Treatment with Dacomitinib and Figitumumab in Advanced Solid Tumors. Clin Cancer Res. 2017 Mar 1;23(5):1177-1185.
• Bahleda R, Grilley-Olson JE, Govindan R, Barlesi F, Greillier L, Perol M, Ray-Coquard I, Strumberg D, Schultheis B, Dy GK, Zalcman G, Weiss GJ, Walter AO, Kornacker M, Rajagopalan P, Henderson D, Nogai H, Ocker M, Soria JC. Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies. Br J Cancer. 2017 Jun 6;116(12):1505-1512.
Rastislav Bahleda
MD
General backgroundAnas Gazzah, MD, Senior Medical Oncologist in the Drug Development Department of Gustave Roussy Cancer Campus since 2010. He received his medical degree from Medical Faculty Sousse Tunisia in 2004. He continued his training to complete a fellowship in Medical Oncology at Paris University VII (Denis Diderot) and VI (Pierre et Marie Curie) from 2005 to 2009.
He completed training in onco-hematology and radiotherapy (2006-2007) and continued his clinical residency training (Institut Gustave Roussy, Assistance Publique Hôpitaux de Paris, Centre René Huguenin).
He continued his clinical research training at Gustave Roussy (2008-2010) and became medical oncologist within the Drug Development Department (Pr Soria) in 2010. Dr Gazzah is board-certified in Medical Oncology since 2009.
Research axes: phase I trials, drug development, targeted and personnalized therapy of lung cancer.
EARLY CLINICAL TRIALS EXPERTISE
ORAL & POSTER PRESENTATIONS
EORTC-NCI-AACR 2016• First-in-human phase I trial of the
anti-CEACAM5 antibody-drug conjugate SAR408701 in patients with advanced
solid tumors (oral)
EORTC-NCI-AACR 2016• Phase Ib study of afatinib plus
standard-dose cetuximab in patients with advanced solid tumours (poster)
ASCO 2015• Phase Ib study of afatinib plus
standard-dose cetuximab in patients (pts) with advanced solid tumors (poster).
PUBLICATIONS
• Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E,
Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J,
Peddareddigari V, Luo FR, Soria J-C. Phase I Dose-Escalation Study of JNJ-
42756493, an Oral Pan–Fibroblast Growth Factor Receptor Inhibitor, in Patients With
Advanced Solid Tumors. J Clin Oncol. 2015;33(30):3401-8.
• Remon J, Gazzah A, Besse B, Soria JC. Crizotinib Improves Osteoarthritis
Symptoms in a ROS1-Fusion Advanced Non-Small Cell Lung Cancer Patient. J
Thorac Oncol. 2015;10(8):e72-73.
• Hollebecque A, Deutsch E, Massard C, Gomez-Roca C, Bahleda R, Ribrag V, Bourgier C, Lazar V, Lacroix L, Gazzah
A, Varga A, de Baere T, Beier F, Kroesser S, Trang K, Zenke FT, Klevesath M,
Soria JC. A phase I, dose-escalation study of the Eg5-inhibitor EMD 534085 in patients with advanced solid tumors
or lymphoma. Invest New Drugs. 2013;31(6):1530-8.
• Gazzah A, Gonzales DB, Levy A, Bahleda R, Ducreux M, Lacroix L,
Soria JC. Molecular guided therapy for advanced pancreatic cancer patients
with PI3K activated mutation: vision or illusion? Onco Targets Ther. 2013; 6:95-7.
• Hollebecque A, Bahleda R, Faivre L, Adam J, Poinsignon V, Paci A, Gomez-
Roca C, Thery JC, Le Deley MC, Varga A, Gazzah A, Ileana E, Gharib M, Angevin
E, Malekzadeh K, Massard C, Soria JC, Spano JP. Phase I study of temsirolimus
in combination with cetuximab in patients with advanced solid tumours. 2017.
European Journal of Cancer 81:81-89.
Anas Gazzah
MD
37
General backgroundJean-Marie Michot is a full-time medical internist at Gustave Roussy. He was first trained in Normandy at the University of Rouen until 2004. He began his training in Paris in 2004 at the University Paris Diderot and obtained a Master 2 specialization in Immunology from the Pasteur Institute of Paris in 2009. He is certified in Internal Medicine and received the Silver Medal from the Faculty of Medicine of Paris in 2010. Dr. Michot is affiliated with the Department of Internal Medicine and Clinical Immunology at University Paris-South Hospital since 2010. He joined the Hematology Unit of Gustave Roussy in 2013 where he developed phase 1 hematology clinical trials with Vincent Ribrag and Stéphane De Botton.
He had a focus for new treatments in lymphoproliferative disorders. His wish is to advance new therapies, and to develop personalized medicine approaches. He aims to improve the management of immunological related adverse events of new immune-checkpoint inhibitors.
EARLY CLINICAL TRIALS EXPERTISE
ORAL PRESENTATIONS
ICML 2017• Phase Ib study of CC-122 in combination with obinutuzumab (GA101): relapsed or refractory (R/R) patients with B-cell non-Hodgkin lymphoma (NHL)
TAT 2017• Phase IB study of CC-122 and obinutuzumab in relapsed or refractory diffuse large B-cell lymphoma and indolent non-Hodgkin lymphoma (oral)
PUBLICATIONS
• Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, Snyder ES, Ricart AD, Balakumaran A, Rose S, Moskowitz CH. Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016 Jun 27. pii: JCO673467 [Epub ahead of print]
• Michot JM, Mazeron R, Dercle L, Ammari S, Canova C, Marabelle A, Rose S, Rubin E, Deutsch E, Soria JC, Ribrag V, Levy A. Abscopal effect in a Hodgkin lymphoma patient treated by an anti-programmed death 1 antibody. Eur J Cancer. 2016;66:91-4.
• Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodriguez MS, Michot JM, Hallek M, Eichhorst B, Reinhardt HC, Bendell J, Derks IA, van Kampen RJ, Hege K, Kersten MJ, Trowe T, Filvaroff EH, Eldering E, Kater AP (2016) Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. Blood. 2016;128(4):574-583.
• Aftimos P, Rolfo C, Rottey S, Offner F, Bron D, Maerevoet M, Soria JC, Moshir M, Dreier T, Van Rompaey L, Michot JM, Silence K, Hultberg A, Gandini D, de Haard H, Ribrag V, Peeters M, Thibault A, Leupin N, Awada A. Phase I Dose-Escalation Study of the Anti-CD70 Antibody ARGX-110 in Advanced Malignancies. Clin Cancer Res. 2017 Nov 1;23(21):6411-6420.
• Zinzani PL, Ribrag V, Moskowitz CH, Michot JM, Kuruvilla J, Balakumaran A, Zhang Y, Chlosta S, Shipp MA, Armand P. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017 Jul 20;130(3):267-270.
Jean-Marie Michot
MD
General backgroundSophie Postel-Vinay (MD, Ph.D), is currently Physician Scientist at the Drug Development Department and U981 INSERM research unit of Gustave Roussy Cancer Campus, where she leads an independent research group as of January 2018 thanks to the ATIP-Avenir INSERM/CNRS grant.
She received her medical degree from the Université René Descartes Paris V in 2010, and joined the faculty in November 2013 after completion of her PhD. She completed her residency training in Paris, and spent 18 months at the Royal Marsden Hospital of London in Pr Stan Kaye Drug Development Unit. Dr Postel-Vinay is member of AACR and ASCO, from which she received a merit award in 2010. She is also an ESMO member, has been representative of the French Young Oncologist at the Young Oncologists Committee from 2013-2016, and received the ESMO translational research fellowship for her PhD that was performed at the Institute of Cancer Research (London) in Pr Alan Ashworth laboratory, focusing on DNA repair and synthetic lethality.
Dr Postel-Vinay has a physician scientist position since 2016, which allows her to have a fundamental research activity within the INSERM Unit 981 (80% of her time), in parallel of her clinical drug development activity (phase 1 trials). She obtained in 2017 the ATIP-Avenir “Young Group Leader” grant from INSERM/CNRS, which now allows her to develop her own group as an independent research team. Her research activity focuses on chromatin remodeling and its interplay with DNA damage repair and immune modulation in solid tumor cancer models. Her research interests include DNA repair, chromatin remodeling and synthetic lethality, sarcoma, drug development, predictive biomarkers and emerging targets.
EARLY CLINICAL TRIALS EXPERTISE
ORAL & POSTER PRESENTATIONS
EORTC-NCI-AACR 2016• First-in-human phase I dose escalation study of the Bromodomain and Extra-Terminal motif (BET)
inhibitor BAY 1238097 in subjects with advanced malignancies (poster)
ESMO ASIA 2015• First-in-human study of oral S 49076, a MET/
AXL/FGFR inhibitor, in advanced solid tumors (poster discussion)
ECCO-ESMO 2013• Towards new methods for the determination of
Dose Limiting Toxicities and Recommended Dose of Molecularly Targeted Agents
PUBLICATIONS
• Infante JR, Hollebecque A, Postel-Vinay S, Bauer TM, Blackwood E, Evangelista M, Mahrus
S, Peale F, Lu X, Sahasranaman S, Zhu R, Chen Y, Ding X, Murray E, Schutzman J, Lauchle JO, Soria
JC, LoRusso PM. Phase I Study of GDC-0425, a checkpoint kinase 1 inhibitor, in combination
with gemcitabine in patients with refractory solid tumors. Clin Cancer Res. 2017 May
15;23(10):2423-2432.
• Postel-Vinay S, Aspeslagh S, Lanoy E, Robert C, Soria JC, Marabelle A. Challenges of phase
1 clinical trials evaluating immune checkpoint-targeted antibodies. Ann Oncol. 2016;27(2):214-
224.
• Postel-Vinay S, Boursin Y, Massard C, Hollebecque A, Ileana E, Chiron M, Jung J, Lee
JS, Balogh Z, Adam J, Vielh P, Angevin E, Lacroix L, Soria JC. Seeking the driver in tumours with
apparent normal molecular profile on comparative genomic hybridiz ation and targeted gene panel
sequencing: what is the added value of whole exome sequencing? Ann Oncol. 2016;27(2):344-52.
• Dercle L, Ammari S, Champiat S, Massard C, Ferte C, Taihi L, Seban RD, Aspeslagh S, Mahjoubi
L, Kamsu-Kom N, Robert C, Marabelle A, Schlumberger M, Soria JC, Postel-Vinay S. Rapid
and objective CT scan prognostic scoring identifies metastatic patients with long-term clinical
benefit on anti-PD-1/-L1 therapy. Eur J Cancer. 2016;65:33-42.
• Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M,
Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in
non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre,
open-label, single-arm first-in-man phase 1 trial.Lancet Oncol. 2017 Dec;18(12):1590-1599.
Rodon J, Postel-Vinay S, Hollebecque A, Nuciforo P, Azaro A, Cattan V, Marfai L, Sudey I, Brendel K,
Delmas A, Malasse S, Soria JC. First-in-human phase I study of oral S49076, a unique MET/AXL/FGFR inhibitor, in advanced solid tumours. Eur J
Cancer 2017. 81:142-150.
Sophie Postel-Vinay
MDPhD
39
General backgroundStéphane Champiat MD, PhDc is currently Assistant Professor at the Drug Development Department of Gustave Roussy Cancer Campus.
He trained at the University of Paris VI medical school and received his medical degree from the University of Nantes in 2014. He completed his residency training in Medical Oncology at the Institute of Cancer Research in Nantes and at Gustave Roussy Cancer Center. He joined the faculty in November 2017.
Dr Champiat worked for one year as a postdoctoral researcher at University California San Francisco focusing on T cell immunity. He started in 2014 a PhD at Paris XI University in the INSERM Unit 981 “Predictive biomarkers and new therapeutic strategies” research group.
He has been working since 2012 at Gustave Roussy where he is growing clinical experience with immunomodulatory antibodies in cancer patients. He is particularly involved in the strategy for managing immune-related toxicities and has setup the immune-related toxicities management program (iTOX program) at Gustave Roussy.
Dr Champiat is a member of the European Society of Medical Oncology (ESMO) and the Society for Immunotherapy of Cancer (SITC).
Research axes: thoracic oncology, early phase studies and cancer immunotherapy.
MD
PUBLICATIONS
• Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, Chaput N, Eggermont A, Marabelle A, Soria JC, Ferté C. HYPERLINK «https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/27827313» Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1. Clin Cancer Res. 2017 Apr 15;23(8):1920-1928.
Michot JM, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S, Berdelou A, Varga A, Bahleda R, Hollebecque A, Massard C, Fuerea A, Ribrag V, Gazzah A, Armand JP, Amellal N, Angevin E, Noel N, Boutros C, Mateus C, Robert C, Soria JC, Marabelle A, Lambotte O. HYPERLINK «https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/26765102» Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016 Feb;54:139-148.
Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F, Cauquil C, Chanson P, Collins M, Durrbach A, Ederhy S, Feuillet S, François H, Lazarovici J, Le Pavec J, De Martin E, Mateus C, Michot JM, Samuel D, Soria JC, Robert C, Eggermont A, Marabelle A. HYPERLINK «https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/26715621» Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol. 2016 Apr;27(4):559-74.
Ederhy S, Voisin A-L, Champiat S. HYPERLINK «https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/28102662» Myocarditis with Immune Checkpoint Blockade.N Engl J Med. 2017 Jan 19;376(3):290-1.
Sun R, Champiat S, Dercle L, Aspeslagh S, Castanon E, Limkin EJ, Baldini C, Postel-Vinay S, Hollebecque A, Massard C, Ammari S, Deutsch E, Soria JC, Marabelle A, Ferté C. HYPERLINK «https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/28826073» Baseline lymphopenia should not be used as exclusion criteria in early clinical trials investigating immune checkpoint blockers (PD-1/PD-L1 inhibitors). Eur J Cancer. 2017 Oct;84:202-211.
Stéphane Champiat
MDPhD
General backgroundCapucine Baldini (MD) is a medical oncologist working at the Drug Development Department (DITEP), Gustave Roussy,Villejuif, France. She is involved in early phase trials with a special interest in geriatric oncology, gastro-intestinal cancer, genito urinary cancer, Central Nervous System tumor.
Dr Baldini received her medical degree from Lille II University in 2014 and got a MSc from PARIS XI University in 2013. She completed her fellowship in medical oncology at Lille University Hospital with a specialization in geriatric oncology and at Gustave Roussy in early phase trials at DITEP. She is a member of ESMO, ASCO, AACR, SIOG, SoFOG and involved in young SIOG and SoFOG interest group leadership. She is working on early phase trials and immunotherapy in older patients.She is a subinvestigator of more than 80 clinical trials (phase 1 trials).
Research axes: early clinical trials, geriatric oncology, GU cancers (prostate cancer, bladder cancer), glioma.
EARLY CLINICAL TRIALS EXPERTISE
RECENT ORAL PRESENTATIONS
IGOM 2017 • Setting up a geriatric oncology unit
ESMO 2017• Immunotherapy phase I trials in patients over 70
years with advanced solid tumours: The Gustave Roussy experience
SIOG 2015• FOLFIRINAGE : Tolerance and efficacy of
FOLFIRINOX in elderly patients with metastatic pancreatic adenocarcinoma
PUBLICATIONS
• Baldini C, Le Saux O, Helissey C, Aspeslagh S, Castanon E, Varga A, Gazzah A, Bahleda R, Mir O, Massard C, Soria JC, Hollebecque A. Are Phase I
trials safe for older patients? J Geriatr Oncol. 2018 Mar;9(2):87-92.
• Loh KP, Soto-Perez-de-Celis E, Hsu T, de Glas NA, Battisti NML, Baldini C, Rodrigues M,
Lichtman SM, Wildiers H. What Every Oncologist Should Know About Geriatric Assessment for
Older Patients With Cancer: Young International Society of Geriatric Oncology Position Paper. J
Oncol Pract. 2018 Feb;14(2):85-94.
• Bigot F, Castanon E, Baldini C, Hollebecque A, Carmona A, Postel-Vinay S, Angevin E, Armand JP, Ribrag V, Aspeslagh S, Varga A, Bahleda R,
Menis J, Gazzah A, Michot JM, Marabelle A, Soria JC, Massard C. Prospective validation of a
prognostic score for patients in immunotherapy phase I trials: The Gustave Roussy Immune Score
(GRIm-Score). Eur J Cancer. 2017 Oct;84:212-218.
• Baldini C, Escande A, Bouché O, El Hajbi F, Volet J, Bourgeois V, Renaut Vantroys T, Ploquin A,
Desauw C, Hebbar M. Safety and efficacy of FOLFIRINOX in elderly patients with metastatic or
locally advanced pancreatic cancer: a retrospective analysis. Pancreatology. 2017 Jan -
Feb;17(1):146-149.
• Mislang AR, Wildes TM, Kanesvaran R, Baldini C, Holmes HM, Nightingale G, Coolbrandt A,
Biganzoli L. Adherence to oral cancer therapy in older adults: The International Society of Geriatric
Oncology (SIOG) taskforce recommendations. Cancer Treat Rev. 2017 Jun;57:58-66.
Capucine Baldini
MD
41
Dr Jean-Pierre Armand focuses his cancer research in the field of new mechanism of oncogenese and early drug development. Jean-Pierre Armand MD, MSc, is certified in Medical Oncology (University of Toulouse III and Paris XI). He is presently senior consultant at Gustave Roussy.
He was General Director of the Institut Claudius Regaud in Toulouse (2007 -2012). Over the last years he has been in charge of the construction of a new cancer center, in a European research hub created in the Toulouse cancer campus (Institut Universitaire du Cancer).
Although expert in breast, head&neck, and neuro-oncology, the first field of Dr Armand was very early drug development in phase 1 and 2. He has been the founder of the IGR Phase I Unit in the early 80s. He did the first in human phase I in the world at IGR of numerous drugs, including classicals cytotoxics, (Irinotecan, Oxaliplatin, Taxotere, Navelbine, Vinflunine), and more recently targeted therapies, (Sutent, Sorafenib, Temsirolismus...)
Prof. Jean-Charles Soria, M.D., Ph.D., is since September 2017, Senior Vice President and Head of the Oncology Innovative Medicines unit (iMED) at MedImmune.
Prof. Soria served as a Professor of Medicine and Medical Oncology at South-Paris University and a Cancer Specialist at Gustave Roussy. Prof. Soria was Chair of the Drug Development Department at Gustave Roussy and was a member of the lung cancer unit with a focus on targeted therapies. His main research interests are early clinical development, phase I trials across solid tumors, pharmacodynamic biomarkers, lung cancer and personalized medicine.
Prof. Soria trained as a medical oncologist and obtained the Silver medal from Paris Medical School in 1997. He gained a PhD degree in the fundamental basis of oncogenesis in 2001, and completed his training with a two-year postdoctoral fellowship in the Department of Thoracic Head and Neck Medical Oncology at MD Anderson Cancer Center, Houston, USA, where he has held an Adjunct Professorship in 2012.
He has contributed to over 550 peer-reviewed publications, including publications as first or last author in the New England Journal of Medicine, Lancet Oncology, JCO, Annals of Oncology. He has been appointed Editor in Chief of Annals of Oncology for 2014-2018.
MD
Jean-Pierre Armand
Jean-Charles Soria
PAST LEADERS IN EARLY DRUG DEVELOPMENT AT GUSTAVE ROUSSY
MD
MDPhD
DITEP EXECUTIVE SUMMARY & DEVELOPMENT PROJECT
Mission/core identity of the DITEPOur mission is to provoke radical changes, qualitative and quantitative strides forward in cancer care.The DITEP team embodies, develops and promotes clinical research that is conceived as patient-centered care and based on offering the greatest number of patients’ access to innovative therapies and to early clinical trials.The innovation is placed at the crossroads between early clinical trials and tumor bio-logy, especially precision medicine.The DITEP is a key player in the develop-ment of immunotherapy, innovative mole-cules in hematological malignancies and combinations to radiotherapy.
Institutional anchoringThe DITEP is structurally and functionally integrated within Gustave Roussy.This integration is implemented as a dyna-mic process of interactions with the other medical departments, research units and technical platforms along the whole drug development path.
Development dynamicsOur goal is to remain in the group of the world leaders in drug development, and to be a key player, driver and facilitator in the evaluation of tomorrow’s medicine in onco-logy.The way to do so is to maintain and to spread enthusiasm, open intelligence and proactive practices regarding future medi-cal and scientific evolutions.
Activity model and quality managementSince November 2016, the DITEP is certi-fied ISO 9001v2015 (Quality Management System) for its activities of access to the-rapeutic innovations, management of early clinical trials, and scientific outreach.Our managerial values are to establish solidarity and cooperation between DITEP professionals and jobs a cornerstone of our practices.The strategic stakes are to ensure and develop the quality of our partnerships, both private and public with industrial and academic teams.
/ DRUG DEVELOPMENT DEPARTMENT
114, rue Édouard-Vaillant94805 Villejuif Cedex - France
Tél. : 01 42 11 42 11Fax : 01 42 11 53 00
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