A national perspective: the French case

Jean-Yves Blay, M.D., Ph.D.,Centre Léon Bérard, Univ Cl. Bernard Lyon I

INNOVATIVE SOLUTIONS FOR RESEARCH IN HEALTHCAREDeveloping a novel approach to deliver better precision medicine in Europe

SESSION II: ROLE OF GOVERNAMENTAL & REGULATORY BODIES

NATIONAL PERSPECTIVE

Individualized medecine for cancer

Genomic platforms & FMG2025

ACSE trials

SIRICs and their programs

Rare cancers

Histology

Nosology and treatment

Stroma(Immune cells, ICP…)

Molecularcharacterisation

Histology

Basket/Umbrella trials

Trials onHistological & molecular

subgroups

Nosology and treatment 2017+

Integrated Dataset: Larotrectinib Is EfficaciousRegardless of Tumor Type1

1. Lanssen U et al. ESMO 2018. Abstract 409O.

Integratedc (n = 109)

ORR, % (95% CI) 81 (72-88)

Best response, %PRCR

6317

Investigator response assessments, as of July 30, 2018

NATIONAL PERSPECTIVE

Individualized medecine for cancer

Genomic platforms & FMG2025

ACSE trials

SIRICs and their programs

Rare cancers

Panels for the analysis of somatic alterations

• INCA Panel: 20 genes with therapeutic implications

• Academic panel(s) : 40-70 gènes

• Commercial panels ( eg FMI): 315 genes

• WES/WGS

• (last 3 reimbursed by RIHN)

Etude ProfilER : diagramme CONSORTEtude ProfilER : diagramme CONSORT

Presented by: O.TREDAN Abstract # LBA100

EnrolledN= 2,676

Tumor genomic profilesN= 1,944

At least one actionable alterationsN= 1,004 (52%)

At least one MTA recommendedN= 676 (35%)

Patients treated with recommendedpersonalized treatment

N= 143 (7%)

Premature withdrawals N= 416 (16%) Tumor sample not exploitable, n= 339

Less than 10% tumor cells, n= 19

DNA extraction issues, n= 19

aCGH or NGS failures, n= 13

Other reasons, n= 31

No recommendation N= 328 (33%) MTA not available, n= 135 MTA previously administered, n= 30 Early death, n= 65 Others, n= 98

The “Plan France Medecine Génomique 2025”Key numbers and facts

approx. 500K whole genomes (200K genomes/yr. at the end of the Plan) > 800 M€ (670M€ + 230M€) 100K patients/yr. at the end of the Plan

12 Very High Throughput sequencing Platforms (18K WG /yr eq. Xten Illumina) One R&D center (CREFIX )

One “Center for data storage and analysis” (CAD)

Focus on cancer & genetic (Mendelian) diseases > multi-factorial diseases

3 pilot projects (colon carcinoma, sarcomas, mental retardation, type2 diabete)

FS/2016

NATIONAL PERSPECTIVE

Individualized medecine for cancer

Genomic platforms & FMG2025

ACSE trials

SIRICs and their programs

Rare cancers

ACSE (NATIONAL, INCA)

NATIONAL PERSPECTIVE

Individualized medecine for cancer

Genomic platforms

ACSE trials

SIRICs and their programs

FMG2025

8 SIRIC FUNDEDExisting sites:• SOCRATE 2.0 : Stratified Oncology Cell dna Repair and Tumor Elimination 2.0

Pr Eric DEUTSCH, Institut Gustave Roussy-VILLEJUIF

• SIRIC Montpellier CancerPr Marc YCHOU, Institut régional du Cancer Montpellier-MONTPELLIER

• INSTITUT CURIE SIRICDr Sergio ROMAN-ROMAN, Institut Curie-PARIS

• BRIO -Bordeaux Recherche Intégrée OncologiePr Pierre-Louis SOUBEYRAN, Institut Bergonié-BORDEAUX

• CARPEM - Cancer Research and Personalized Medicine PARISPr Pierre LAURENT-PUIG, Hôpital Européen Georges Pompidou-HEGP AP-HP-PARIS

New sites:• ILIAD-Imaging and Longitudinal Investigations to Ameliorate Decision making in multiple

myeloma and breast cancer NANTES -ANGERSPr Philippe MOREAU, CHU Nantes - Hôtel Dieu-NANTES

• CURAMUS-Cancer United Research Associating Medicine, University & Society PARISPr Marc SANSON, Groupe Hospitalier Pitié Salpétrière-PARIS

INCa, Inserm and DGOS support and financing

FROM LYric TO LYriCAN

Cancer cellsand immune

targets

Combiningtreatments to

preventresistance

PhysicalAgents

Overcoming cellplasticity

Tumorcell

Macro-scopictumor

Immunothera

py

New targetsand

treatments

Personalised medicinebased on genomic

context

DevWeCan,PlasCan

TumAdoR,Hermione2Man

Personalized medicine based ongenomic context and

tumoral heterogeneity

AURAGEN,EURACAN,SSH Chair

ProfiLERMOST

BASIC RESEARCH

NATIONAL PERSPECTIVE

Individualized medecine for cancer

Genomic platforms & FMG2025

ACSE trials

SIRICs and their programs

Rare cancers

Clinical networks for rare cancersCancers rares Nom du

réseauCoordonnateurnational (et co-coordonnateurs)

Centre expertnational(un ou plusieurs sites)

Sarcomes des tissus mous et desviscères

NETSARC Pr Jean-Yves BlayDr Binh BuiDr Axel Le Cesne

Centre Léon BérardInstitut BergoniéInstitut GustaveRoussy

Sarcomes osseux RESOS Pr François Gouin CHU de NantesTumeurs neuroendocrines malignesrares

RENATEN Pr Patricia Niccoli Hôpital de la Timone,AP-HM

Tumeurs cérébrales rares TUCERA Pr Hugues Loiseau Hôpital Pellegrin,CHU de Bordeaux

Tumeurs oligodendrogliales de hautgrade

POLA Pr Jean-YvesDelattrePr DominiqueFigarella-Branger

Hôpital Pitié-Salpêtrière, AP-HPHôpital de la Timone,AP-HM

Cancers cutanés rares CARADERM Pr Laurent Mortier CHRU de Lille

Cancers ORL rares REFCOR Dr François JanotPr Baujat

Institut GustaveRoussyHôpital Tenon, AP-HP

Thymomes malins et carcinomesthymiques

RYTHMIC Dr Benjamin BessePr Nicolas Girard

Institut GustaveRoussy, Hôpital LouisPradel, HCL

Mésothéliomes malins pleuraux MESOCLIN Pr ArnaudScherpereelPr Françoise LePimpec-BarthesPr Jacques Margery

CHRU LilleHôpital EuropéenGeorges Pompidou,AP-HPInstitut GustaveRoussy

Bone

Soft tissue

Visceral

NetSARC: a network of 26 sarcoma reference centers in France35784 pts with follow-up presented in MDT since 2010

• 26 centers of reference in Netsarc• Linked with Pathology network (RREPS)• Linked with Bone Network RESOS (2014)

• 3 networks to be merged (2019)

• Single website

• Entry in the site by CRAs• Not a clinical trial, a registry

• Aims:• Guidelines• Guiding best practices/patient pathways• Measuring• Research

Soft tissue

LRFS & OS : incident patient populationN=35784 sarcoma patients

Operated- In NETSARC, N=9910 (33.9%)- Outside NETSARC, N=19307 (66.1%)

P<0.0001 P<0.0001

Now this is not the end.It is not even the beginning of the end.

But it is, perhaps, the end of the beginning.

ConclusionsNational initiatives

Molecular platforms

Basket trials

Sites of innovative research (SIRICs)

Larger panels/platforms : are they better?

Nationwide with FMG2025

Initial treatment in curative phases