Personaldlized Medicine in Cancer · lamp1 lck lifr lphn3 lpp lrp1b ltf ltk maf mafb magea1 magi1...

l d dPersonalized Medicine in Cancer

Mohammad Ali SaremiMohammad Ali Saremi(Ph.D.)

Personalized Medicine

Effectiveness of drugs:Effectiveness of drugs:

Danger of drugs:

• 6.7% of patients in hospitals experience serious6.7% of patients in hospitals experience serious drug reactions

Old Paradigm:Old Paradigm:

New Paradigm:New Paradigm:

Future Paradigm:Future Paradigm:

PharmacogenomicsPharmacogenomics

Does one size really fit all?

PharmacogeneticsPharmacogenetics

• Study of genetic variation that gives rise to y g gdifferent responses to drugs

• It is estimated that genetics can account for 20It is estimated that genetics can account for 20 to 95 percent of variability in drug disposition and effectsand effects.

• Nongenetic factors include: age, organ function, concomitant therapy drug interactions and theconcomitant therapy, drug interactions, and the nature of the disease.

Pharmacogenomics – Under the PM b llUmbrella

• Better medication choices– 100,000 Americans die annually and 2,000,000+ are hospitalized due to adverse reactions to medications

– Predict individual reactions to dugs

• Safer dosing options– More exact dosing, optimum result/side effect balance

• Improvements in drug developmentp g p– Exclude genetic variations from certain clinical trials, speeding up drug design time

1 OncoDNA in a few words1. OncoDNA in a few words2. What is OncoDEEP ?3 Case studies using3. Case studies using

OncoDEEP4 What is OncoSHARE ?4. What is OncoSHARE ?5. Aurora Program

Mission / Vision

A better characterization of the patient and his disease for a better treatment establishment and follow-up

OncoDNA is a Cancer Theranostics Company bringing a unique combination of the most relevant technologies (mostly Next GenerationSequencing (NGS) and protein biomarker analyses (IHC)) to support physician/oncologist with treatment regimen establishment

Our goal is to predict and follow the response to anticancer drugsOur goal is to predict and follow the response to anticancer drugswith a comprehensive and integreted (genomic – anatomopathologic) approach.

OncoDNA in a few words

Creation: November 2012

Shareholders• Institute of Pathology and Genetics (Gosselies & Brussels, Belgium) Institute of Pathology and Genetics (Gosselies & Brussels, Belgium)

• 280 people• 270 000 analyses / year• 3rd European laboratory for cancer analyses (anatomical pathology)

• Sambrinvest Regional Private Equity and Venture Capital Firm• Business Angels

Scientific Council• Prof Martine Piccart - President of the European Society for Medical Oncology (ESMO)• Prof Jaak Janssens - President at Interventional Oncology Society

D Ch i t S ti i H d t B t C T l ti l L b t J C H• Dr Christos Sotiriou - Head at Breast Cancer Translational Laboratory J-C Heuson• Prof Jean-Pascal Machiels - Centre du Cancer (UCL)

OncoDNA : key facts

OncoDEEP DX (v2: 60 genes) and Clinical (409 genes) are ISO15189OncoDEEP DX (v2: 60 genes) and Clinical (409 genes) are ISO15189 accredited since 2013 (CE IVD marked and CLIA certification in process)

Development of Package Plus based and updated with latestDevelopment of Package Plus based and updated with latestpublications

More than 1000 samples processed from 25 countries worldwide and of more than 40 cancer typesof more than 40 cancer types

Selected by Breast Interfor for the AURORA project (around 4000 samples from 1300 patients to be sequenced with OncoDEEP Clinical+ BRCA1/2 + Small Breast Cancer Specific Package Plus)

Proprietary algorithm for CNV detections recently published in Bioinformatics

OncoDEEP DX v2 released end of Summer along with Fusion Gene Panel

OncoTRACE (RUO): circulating tumoral DNA monitoring

From research to diagnostic : first diagnostic application

CCancer : Multigenic Disease

Huge expertise at IPG (3rd European laboratory for cancer analyses)laboratory for cancer analyses)

Cancer known to be a genomic disease

Refers to at least 100 forms of disease

The field for the development of perzonalized treatments

Di ith hi h i id dDisease with very high incidence and mortality

What is OncoDEEP ?

Choice of the treatment after complete pmolecular characterization of patient’stumor sample.

Cancer Cancer treatmenttreatment historyhistory parallelparallel to cancer to cancer knowledgeknowledge developmentdevelopment

Growth signal inhibitors

Angiogenesis inhibitorsEarly times of targeted therapies

Target a specificidentified

Apoptosis‐inducing drugs

targeted therapies cause of the cancer

Example

BCR BCR –– ABL ABL Fusion GeneFusion Gene

Imatinib(Gleevec)

Chronic Chronic MyelogenousMyelogenousLeukemia (CML) Leukemia (CML)

Cancer Cancer treatmenttreatment historyhistory parallelparallel to cancer to cancer knowledgeknowledge developmentdevelopmentTodays’ view on cancer molecular network and on drugs which could

interact with these pathways for cancer treatment

Oncologists Need a NewOncologists Need a New Molecular Analysis Tool to

mTORinhibitors

3

KIT inhibitors

EGFR inhibitors

ERBB2

EGFR inhibitors

ERK

JAK inhibitors

STAT3

IGF1R inhibitors

PDGFR

yBetter Characterize

k

PI3‐kinase

inhibitors

ERBB2 inhibitors

ERBB3 inhibitors

ERK inhibitors

MEK inhibitors

FGFR inhibitors

STAT3inhibitors

PDGFR inhibitors

Prostate Cancer: up and down regulated molecular pathways

Patient’s Tumor !!Akt

inhibitors ERBB4 inhibitors

inhibitorsinhibitors regulated molecular pathwaysnetwork in diseasedconditions

What is OncoDEEP ?

NGS analysis + Package Plus

IHC analyses Additional analyses+

EGFR proteinexpression positive

Cetuximab

BRAF V600E mutation positive

Dabrafenib

MGMT promotermethylation

Temozolomide

What is OncoDEEP ?


To search drug actionable mutations in the genome of tumoral cells

What is OncoDEEP ?


To search drug actionable mutations in the genome of tumoral cells

Comprehensive and non supervised search for variants

Using Next Generation Sequencing: Powerful and Sensitive method to search variants

At very high coverage to help avoiding false positive and false negativeAt very high coverage to help avoiding false positive and false negative

Ion Torrent allows a very fast turn around time to allow fast treatment decision

ABL1 ABL2 ACVR2A ADAMTS20 AFF1 AFF3 AKAP9 AKT1 AKT2 AKT3ALK AMER1 APC AR ARID1A ARID2 ARNT ASXL1 ATF1 ATM

What is OncoDEEP ?ABL1 ABL2 ACVR2A ADAMTS20 AFF1 AFF3 AKAP9 AKT1 AKT2 AKT3ALK AMER1 APC AR ARID1A ARID2 ARNT ASXL1 ATF1 ATMALK AMER1 APC AR ARID1A ARID2 ARNT ASXL1 ATF1 ATM

ATR ATRX AURKA AURKB AURKC AXL BAI3 BAP1 BCL10 BCL11ABCL11B BCL2 BCL2L1 BCL2L2 BCL3 BCL6 BCL9 BCR BIRC2 BIRC3BIRC5 BLM BLNK BMPR1A BRAF BRD3 BRIP1 BTK BUB1B CARD11CASC5 CBL CCND1 CCND2 CCNE1 CD79A CD79B CDC73 CDH1 CDH11CDH2 CDH20 CDH5 CDK12 CDK4 CDK6 CDK8 CDKN2A CDKN2B CDKN2C

CEBPA CHEK1 CHEK2 CIC CKS1B CMPK1 COL1A1 CRBN CREB1 CREBBPCRKL CRTC1 CSF1R CSMD3 CTNNA1 CTNNB1 CYLD CYP2C19 CYP2D6 DAXX

ALK AMER1 APC AR ARID1A ARID2 ARNT ASXL1 ATF1 ATMATR ATRX AURKA AURKB AURKC AXL BAI3 BAP1 BCL10 BCL11A

BCL11B BCL2 BCL2L1 BCL2L2 BCL3 BCL6 BCL9 BCR BIRC2 BIRC3BIRC5 BLM BLNK BMPR1A BRAF BRD3 BRIP1 BTK BUB1B CARD11CASC5 CBL CCND1 CCND2 CCNE1 CD79A CD79B CDC73 CDH1 CDH11CDH2 CDH20 CDH5 CDK12 CDK4 CDK6 CDK8 CDKN2A CDKN2B CDKN2C

CEBPA CHEK1 CHEK2 CIC CKS1B CMPK1 COL1A1 CRBN CREB1 CREBBPCRKL CRTC1 CSF1R CSMD3 CTNNA1 CTNNB1 CYLD CYP2C19 CYP2D6 DAXX

DCC DDB2 DDIT3 DDR2 DEK DICER1 DNMT3A DPYD DST EGFREML4 EP300 EP400 EPHA3 EPHA7 EPHB1 EPHB4 EPHB6 ERBB2 ERBB3

ERBB4 ERCC1 ERCC2 ERCC3 ERCC4 ERCC5 ERG ESR1 ETS1 ETV1ETV4 EXT1 EXT2 EZH2 FANCA FANCC FANCD2 FANCF FANCG FAS

FBXW7 FGFR1 FGFR2 FGFR3 FGFR4 FH FLCN FLI1 FLT1 FLT3FLT4 FN1 FOXL2 FOXO1 FOXO3 FOXP1 FOXP4 FZR1 G6PD GATA1

GATA2 GATA3 GDNF GNA11 GNAQ GNAS GPR124 GRM8 GUCY1A2 HCAR1HIF1A HLF HNF1A HOOK3 HRAS HSP90AA1 HSP90AB1 ICK IDH1 IDH2

DCC DDB2 DDIT3 DDR2 DEK DICER1 DNMT3A DPYD DST EGFREML4 EP300 EP400 EPHA3 EPHA7 EPHB1 EPHB4 EPHB6 ERBB2 ERBB3ERBB4 ERCC1 ERCC2 ERCC3 ERCC4 ERCC5 ERG ESR1 ETS1 ETV1ETV4 EXT1 EXT2 EZH2 FANCA FANCC FANCD2 FANCF FANCG FAS

FBXW7 FGFR1 FGFR2 FGFR3 FGFR4 FH FLCN FLI1 FLT1 FLT3FLT4 FN1 FOXL2 FOXO1 FOXO3 FOXP1 FOXP4 FZR1 G6PD GATA1

GATA2 GATA3 GDNF GNA11 GNAQ GNAS GPR124 GRM8 GUCY1A2 HCAR1HIF1A HLF HNF1A HOOK3 HRAS HSP90AA1 HSP90AB1 ICK IDH1 IDH2

OncoDEEP DX OncoDEEP ClinicalHIF1A HLF HNF1A HOOK3 HRAS HSP90AA1 HSP90AB1 ICK IDH1 IDH2IGF1R IGF2 IGF2R IKBKB IKBKE IKZF1 IL2 IL21R IL6ST IL7RING4 IRF4 IRS2 ITGA10 ITGA9 ITGB2 ITGB3 JAK1 JAK2 JAK3JUN KAT6A KAT6B KDM5C KDM6A KDR KEAP1 KIT KLF6 KRAS

LAMP1 LCK LIFR LPHN3 LPP LRP1B LTF LTK MAF MAFBMAGEA1 MAGI1 MALT1 MAML2 MAP2K1 MAP2K2 MAP2K4 MAP3K7 MAPK1 MAPK8MARK1 MARK4 MBD1 MCL1 MDM2 MDM4 MEN1 MET MITF MLH1

MLL MLL2 MLL3 MLLT10 MMP2 MN1 MPL MRE11A MSH2 MSH6

HIF1A HLF HNF1A HOOK3 HRAS HSP90AA1 HSP90AB1 ICK IDH1 IDH2IGF1R IGF2 IGF2R IKBKB IKBKE IKZF1 IL2 IL21R IL6ST IL7RING4 IRF4 IRS2 ITGA10 ITGA9 ITGB2 ITGB3 JAK1 JAK2 JAK3JUN KAT6A KAT6B KDM5C KDM6A KDR KEAP1 KIT KLF6 KRAS

LAMP1 LCK LIFR LPHN3 LPP LRP1B LTF LTK MAF MAFBMAGEA1 MAGI1 MALT1 MAML2 MAP2K1 MAP2K2 MAP2K4 MAP3K7 MAPK1 MAPK8MARK1 MARK4 MBD1 MCL1 MDM2 MDM4 MEN1 MET MITF MLH1

MLL MLL2 MLL3 MLLT10 MMP2 MN1 MPL MRE11A MSH2 MSH6

50 65 genes

Actionnable

409 genespathway‐basedgene selection

MTOR MTR MTRR MUC1 MUTYH MYB MYC MYCL1 MYCN MYD88MYH11 MYH9 NBN NCOA1 NCOA2 NCOA4 NF1 NF2 NFE2L2 NFKB1NFKB2 NIN NKX2-1 NLRP1 NOTCH1 NOTCH2 NOTCH4 NPM1 NRAS NSD1NTRK1 NTRK3 NUMA1 NUP214 NUP98 PAK3 PALB2 PARP1 PAX3 PAX5PAX7 PAX8 PBRM1 PBX1 PDE4DIP PDGFB PDGFRA PDGFRB PER1 PGAP3

PHOX2B PIK3C2B PIK3CA PIK3CB PIK3CD PIK3CG PIK3R1 PIK3R2 PIM1 PKHD1PLAG1 PLCG1 PLEKHG5 PML PMS1 PMS2 POT1 POU5F1 PPARG PPP2R1APRDM1 PRKAR1A PRKDC PSIP1 PTCH1 PTEN PTGS2 PTPN11 PTPRD PTPRT

MTOR MTR MTRR MUC1 MUTYH MYB MYC MYCL1 MYCN MYD88MYH11 MYH9 NBN NCOA1 NCOA2 NCOA4 NF1 NF2 NFE2L2 NFKB1NFKB2 NIN NKX2-1 NLRP1 NOTCH1 NOTCH2 NOTCH4 NPM1 NRAS NSD1NTRK1 NTRK3 NUMA1 NUP214 NUP98 PAK3 PALB2 PARP1 PAX3 PAX5PAX7 PAX8 PBRM1 PBX1 PDE4DIP PDGFB PDGFRA PDGFRB PER1 PGAP3

PHOX2B PIK3C2B PIK3CA PIK3CB PIK3CD PIK3CG PIK3R1 PIK3R2 PIM1 PKHD1PLAG1 PLCG1 PLEKHG5 PML PMS1 PMS2 POT1 POU5F1 PPARG PPP2R1APRDM1 PRKAR1A PRKDC PSIP1 PTCH1 PTEN PTGS2 PTPN11 PTPRD PTPRT

g

PRDM1 PRKAR1A PRKDC PSIP1 PTCH1 PTEN PTGS2 PTPN11 PTPRD PTPRTRAD50 RAF1 RALGDS RARA RB1 RECQL4 REL RET RHOH RNASELRNF2 RNF213 ROS1 RPS6KA2 RRM1 RUNX1 RUNX1T1 SAMD9 SBDS SDHASDHB SDHC SDHD SEPT9 SETD2 SF3B1 SGK1 SH2D1A SMAD2 SMAD4

SMARCA4 SMARCB1 SMO SMUG1 SOCS1 SOX11 SOX2 SRC SSX1 STK11STK36 SUFU SYK SYNE1 TAF1 TAF1L TAL1 TBX22 TCF12 TCF3

TCF7L1 TCF7L2 TCL1A TET1 TET2 TFE3 TGFBR2 TGM7 THBS1 TIMP3TLR4 TLX1 TNFAIP3 TNFRSF14 TNK2 TOP1 TP53 TPR TRIM24 TRIM33

PRDM1 PRKAR1A PRKDC PSIP1 PTCH1 PTEN PTGS2 PTPN11 PTPRD PTPRTRAD50 RAF1 RALGDS RARA RB1 RECQL4 REL RET RHOH RNASELRNF2 RNF213 ROS1 RPS6KA2 RRM1 RUNX1 RUNX1T1 SAMD9 SBDS SDHASDHB SDHC SDHD SEPT9 SETD2 SF3B1 SGK1 SH2D1A SMAD2 SMAD4

SMARCA4 SMARCB1 SMO SMUG1 SOCS1 SOX11 SOX2 SRC SSX1 STK11STK36 SUFU SYK SYNE1 TAF1 TAF1L TAL1 TBX22 TCF12 TCF3TCF7L1 TCF7L2 TCL1A TET1 TET2 TFE3 TGFBR2 TGM7 THBS1 TIMP3TLR4 TLX1 TNFAIP3 TNFRSF14 TNK2 TOP1 TP53 TPR TRIM24 TRIM33

TRIP11 TRRAP TSC1 TSC2 TSHR UBR5 UGT1A1 USP9X VHL WASWHSC1 WRN WT1 XPA XPC XPO1 XRCC2 ZNF384 ZNF521

TRIP11 TRRAP TSC1 TSC2 TSHR UBR5 UGT1A1 USP9X VHL WASWHSC1 WRN WT1 XPA XPC XPO1 XRCC2 ZNF384 ZNF521

Genes in OncoDEEP DX Genes in OncoDEEP Clinical

OncoDeep® Data Analysis Process

Less False PositivelLess False Negative

ReportingWhat is OncoDEEP ?

VARIANT TYPES REPORTED

Inherited Variants

Actionable variants With Biological, Clinical

Inherited Variants

Medically actionable

Not reported as Germinal Variant but as variant with potential g

and Therapeutical impactMedically actionableincidental findings

variant with potentialhereditary impact to bechecked in non‐tumoral sample (e.g. blood)

Variants of UncertainP l hi Variants of UncertainSignificance (VUS)

Polymorphism

Not just polymorphism b t ith t ti l

Benign polymorphism without biological and but with potential

biological and clinical impact

without biological and clinical impact

OncoDEEP Reporting: Variant analysis

α‐ListBiomarkers

related to Drug gLabel are paid a

specific attention withattention with manual check of aligned reads raw data

What is OncoDEEP ?

NGS analysis ++ Package Plus

IHC analyses Additional analyses+

To look at final cellular effectorsquantity and/or activity

What is OncoDEEP ?


IHC analyses Additional analyses+A l f 5 t 8 IHC

IHC specific of the analyzed cancer type

A panel of 5 to 8 IHCsTo look at final cellular effectors

quantity and/or activity

Looking at presence (IHC) and activation

Addressing chemotherapy, targetedtherapy and pathway biomarkers

Looking at presence (IHC) and activation of proteins (Phospho‐IHC)

What is OncoDEEP ?


IHC analyses Additional analyses+Targeted Cancer Specific

PTENC‐METAEG‐1

Targeted

Chemotherapy From the shelf

Ca ce Spec c

Ki‐67ER

e.g. Breast cancer:

PDL1Phospho‐4EBP1Phospho‐S6Phospho‐AKT

ERCC1

RRM1

ERPRTLE3TS

PDL1Topo1EGFR

β‐CATENINTUBB3Phospho‐ERK1/2 Top2A

Her2

βTUBB3

What is OncoDEEP ?


IHC analyses Additional analyses+Because some cancer biomarkers are very specific !!

What is OncoDEEP ?


IHC analyses Additional analyses+Because some cancer biomarkers are very specific !!

Breast Cancer: FISH Analysis for Her2‐Neu Amplification Trastuzumab (Herceptin®)p

Hereditary NonPolyposis CR Cancer: Multiplex PCR for Microsatellite Instability

No Benefit of adjuvant 5‐FU‐based chemotherapy

NSC Lung Cancer: ALK‐EML4 Translocation Crizotinib (Xalkori)

Genomic test in routineGenomic test in routine Gender : FemaleO BOrgan : BreastTumor type : Advanced breast carcinomaSpecimen : FFPE SLIDE

FISH and IHC HER2 positive

Relapse under Herceptin treatment

Patient was getting worse very fast

Lapatinib

OncoDEEP ClinicalOncoDEEP Clinical

Detection of the L755S variant in HER2, which is knownto be Lapatinib resistant

Confirmation of HER2 Amplification

to be Lapatinib resistant

Patient oriented towards a clinical trial associated with new HER2 inhibitor whose mechanism is not based on Lapatinib mechanism

OncoDEEP DXOncoDEEP DX GenderGender : FemaleO B C

But discovery of CDKN2A d l ti

No variant identified Organ : Breast CancerTumor type : ER/PR‐positive ‐ HER2‐negativeTreatment : Neo‐adjuvant therapyClinic : Residual disease observed

C 2 d l ia CDKN2A deletion after surgeryCDKN2A deletion

CDK4/6 : Therapy target ?

Clinicaltrial govClinicaltrial.govNCT01864746PENELOPE‐B

A di t i f ti

CELL PROLIFERATION

According to our information, patient has been enrolled on the

basis of OncoDEEP results

What is OncoSHARE ?

OncoSHARE is a Web interface which allows:

A comprehensive listing of all variant findings. Imagine a paper listing of around 250 p g g g p p gvariants found in a OncoDEEP Clinical listed with all biological, clinical and therpeutical information listedin a pdf document ….

A detailed and interactive presentation of drug recommendations and clinical trials availability along with all related publication directly accessible throughhyperlinks

An easy sharing of the report by oncologists, with colleague(s), withMolecular Board or with Expert of the field [, with Patient]

OncoDEEP - OncoSHARE: How it works ?

Analysis Ordering & Sample Shipment

1TecP

roReports

2

5 hnical ocess

Reports exchanges

between oncologists and

Data analysis

gwhen allowed,

with patients3

yand integration

Reporting4


Analysis Ordering &1

These Kits a barcoded and can ship FFPE

Analysis Ordering & Sample Shipment

1

These Kits a barcoded and can ship FFPEtumor block and slides in cartridge.

Kits also contain shipping bag and prefilled waybill for safe and FREE p yshipment

O l i l it i d d iOn sample arrival, it is encoded in our OncoLIMS for technical processes


Analysis Ordering & Sample Shipment1 Analysis Ordering & Sample Shipment1

R d d iRecommanded pricesstarting from Belgium

OncoDEEP ‐ OncoSHARE: How it works ?

Sample ReceptionSample Reception(FFPE)

3 4 days TAT

Technical Process2

AnapathReviewand QC

Do not reachQuality Criteria=>

Stop

DNA Extraction + OncoDEEP Sequencing

Reach QualityCriteria

3‐4 days TAT

+ Package testing(Immuno, Fish…)

Bioinformatics + Gene analysis

1‐2 days TAT

Reporting(DX – Clinical)

1‐2 days TAT

7 to 10 days delivery time

Final comprehensiveReport including analyses

and final conclusions

Confirmation by classical testing if required (FISH, …)

7 to 10 days delivery time

and final conclusions


Data analysis and integration3 and integration

K l dEMA

KnowledgeDataBaseOncoDNA

The image part with relationship ID rId6 was not found in the file.

Web reporting


Pathology Reporting4Pathologyreport

Reporting

List of variants discovered with NGSand their impact

Process summary

List of drugs recommended for the specific conditions of the patient

Process summary

Package Plus results

List of clinical trials available for patients’ specific conditions List of publications

related to report findings


Reporting4


Reporting4 Reporting4

OncoDEEP ‐ OncoSHARE: How it works ? Drug recommendation

In Indication

Out of Indication

In Development


R ti4

Drug recommendation

Reporting4

General drugdescription

Drug description in the sepcific cancer

type context

Clinicaldevelopment stage


R ti4

Drug recommendation

Reporting4


Reporting4 p g

OncoDEEP PHARMA : One product – Four Options

OncoDeep® : Challenges

P i dP i dPrecious and limitedmaterial

Precious and limitedmaterial

Integration of results from NGS IHCsIntegration of results from NGS IHCs

FFPE Bl k

Integration of results from NGS, IHCsand anathomopathology testing isneeded to have a multidimensional

overview of the tumor

Integration of results from NGS, IHCsand anathomopathology testing isneeded to have a multidimensional

overview of the tumor

Turn around time is a priority

Turn around time is a priority

FFPE Block

Sample isheterogenous, not only tumor cells

Sample isheterogenous, not only tumor cells

Processes are multiple and require several

expertices

Processes are multiple and require several

expertices

DNA is degradedDNA is degraded

WeWe have have developpeddevelopped a one stop solutiona one stop solution

OncoDEEP and AURORA

The Breast International Group (BIG): p ( )‐ A non‐profit organisation for breast cancer research ‐ 49 collaborative groups from around the world‐ About 30 clinical trials are run or are under

development‐ Works closely with the US National Cancer Institute

(NCI) and the North American Breast Cancer Group (NABCG)(NABCG)

‐ European based, Headquartered in Brussels

Major financer is The Breast Cancer Research Foundation (USA)

Martine J. Piccart, MD, PhD, Speaking about OncoDNA and AURORA

WHY Metastatic Breast Cancer (MBC) ?

The disease remains incurable ... Despite 3 decades of research efforts

The median survival of these women remains poor: about 30 months

Unprecedented opportunity to make more rapid progress, using OncoDEEP Clinical Plusp g , g

Newly diagnosed or

‘Actionable’ Mutation(s) (n˷300)

‘Actionable’ Mutation(s) (n˷300)

N=1,300N=1,300

d ag osed o1st Line MBC Patients

Downstream TargetedClinical Trials

as first or second line

Downstream TargetedClinical Trials

as first or second line

Clinical Outliers(Exceptional

Responders and RapidN 1,300N 1,300

‘Non‐Actionable’ Mutations (n˷700)‘Non‐Actionable’ Mutations (n˷700) Standard of CareStandard of Care

Screening Failuren=300

pProgressors) to be subjected to

WES

Continue until disease progression

Timeline

DiseaseProgression

Entry in DCT Cycle 1 Cycle 3 Cycle X

….Cycle 2

Metastatic Lesion Biopsy – TGS (real time) and RNAseq (on batches)

Primary Tumour Archival – TGS (real time) and RNAseq (on batches)

Pl /S

Blood TGS (real time)

Plasma/Serum Collection every 6 months – up to 10 years

Clinical OutcomeInformation Collection every 6 months – up to 10 years

Program ‐ Protocol

OBJECTIVESTo improve the understanding of MBC by performing high coverage TGS and RNA sequencing on matched primary and metastatic samples to explore tumor heterogeneity, clonal evolution and transcriptional changes associated with mutational and CNV patterns.

To discover biomarkers of response and/or resistance to systemic therapy using genomic and transcriptomic dataTo discover biomarkers of response and/or resistance to systemic therapy using genomic and transcriptomic data of “exceptional responders” and “rapid progressors”.

To build new therapeutic hypotheses based on findings generated by TGS.

To evaluate the prognostic relevance of genomic alterations detected in tumour metastatic biopsies and archived p g g pprimary tissue.

To correlatemolecular alterations in patients with the efficacy endpoints (response rate, progression‐free survival (PFS) and OS).

To identify patients with candidate driver alterations in their tumours that can be matched to biomarker‐driven clinical trials.


WHY having chosen OncoDNA ?

OncoDNA has participated, without knowing about it, to a pilot trial of 30 MBC samples tested using OncoDEEP Clinical.p g

Data generated were compared, blind, to data generated by the Sanger platform, 1 other academic lab and one other vendor (not di l d)disclosed).

1) Data quality and robustness on those very small metastasis biopsies and 2) delivery time were the major two differenciating factors.

«OncoDNA has been chosen because it offers a real professional and quality service»

) y j g


What does OncoDNA do in AURORA?

Next Generation Sequencing analysis of our Clinical panel (409) along with NGS analysis of BRCA1‐2

ImmunoHistoChemistry analysis of ER, PR, HER2 and Ki‐67. Slide digitalization and image archiving.

T bi b ki f FFPE l f bi i d bl d

FISH analysis of HER2 in case of IHC HER2 3+

Temporary biobanking of FFPE samples, frozen biopsies and blood sample.

Potential future work (depending of financing availability) WESPotential future work (depending of financing availability): WES (Whole exome sequencing), WTS (Whole transcriptome sequencing);

Quality Assurance

IS015189 for IPG (Medical laboratories — Particular requirements for quality and competence: specifying the quality management system requirements particular to medical laboratories)

ISO17025 for Bio.be

GCLP Compliant – Audited by from pharma partners

(The main ISO/CASCO standard used by testing and calibration laboratories)

GCLP Compliant Audited by from pharma partners

CLIA/CAP Certification in process

Official biobank for Belgian National Cancer Plan (IPG)

Official Belgian Genetics Centre (IPG)

IVD marking according to Directive 98/79/ECIVD marking according to Directive 98/79/EC

Partners

کنگره سرطان و پيشگيری ١٣٩٣بھمن ماه ٧و ۶

سيما و صدا المللی بين ھمايشھای سالن ھمايشھای بين المللی صدا و سيماسالن

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Personaldlized Medicine in Cancer · lamp1 lck lifr lphn3 lpp lrp1b ltf ltk maf mafb magea1 magi1...

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