10-martinzoche-expusz-fmi journ e seq-gfco 11102017xe9e%20ngs%2011%20... · martin zoche, gfco, oct...

FoundationOne

The Swiss Experience at the University Hospital Zurich

Martin Zoche GFCO, Oct 11, 2017

2Martin Zoche, GFCO, Oct 11, 2017

Disclosures

Martin Zoche has no conflict of interest.


Improving Personalized Healthcare @ USZCancer patient diagnostic testing in an academic

setting

79% 21%

2 TESTSfor diagnosis

3-15 TESTSfor diagnosis

8,020 Patients2014-2016


EGFR, KRAS neg

1,013 CHF

03.2015

ALK neg

931 CHF

12.2015

ERBB2 neg

1,478 CHF

12.2015

BRAF neg

547 CHF

04.2016

MET, MYK pos

2,419 CHF

05.2016

TISSUE

5x

TIME

14months

TOTAL COST

6400 CHFHIT & MISS HOT-SPOT

Example: Lung Cancer PatientIterative testing vs one comprehensive genomic profile


Strategic Partnership between FMI, Roche and

the UniversityHospital Zurich

Phase 1 Launch

offering Foundation

Medicine services through

the USZ since Jan 2017

First FMI /

Academic lab collaboration

worldwide

Establish academic

partnership

with University Hospital Zurich

in collaboration with Pharma,

Diagnostics and FMI

Local lab to ensure broad

access for clinical routine and

for research

Pharma & Diagnostics


FMI Current Service OverviewIterative testing vs one comprehensive genomic profile

315 cancer-related genesknown to be drivers ofsolid tumorsSelected introns of 28 genes

405 genes and RNA sequence (cDNA) information

of 265 commonly rearranged genes in hematol. tumors

A liquid biopsy assay for Circulating Tumor DNA

62 genes known to be drivers of solid tumors

Mircrosatellite Instability (MSI)Tumor Mutaional Burden (TMB)

• A single solution for simulteaneous assessment of MSI and TMB

• Provide relevant genomic information for immunotherapies


missed

CATEGORY ONE

CATEGORY TWO

CATEGORY THREE

Routine single

marker molecular

tests such as IHC,

PCR and FISH

Single-Marker Test

foundmissed missed

missed


CATEGORY ONE

CATEGORY THREE

CATEGORY TWO

Identify pre-

specified mutations

occurring in limited

areas of genes of

interest.

Multi-gene

"Hot Spot" Test

foundfound

foundmissedmissed


CATEGORY TWO

CATEGORY ONE

FMI’s

comprehensive

genomic profiling

approach of

testing all of the

known clinically

relevant cancer

genes

CATEGORY THREE

Comprehensive

Genomic Profiling

foundfound foundfound

found


Copy number

alterations

Base

substitutions

Rearrangements

(gene fusions)

Unaltered

chromosome

Gene of

interest

Insertions and

deletions

Class of genomic alteration

There are four classes of genomic alteration that can drive tumor growth. All classes may be

clinically relevant because they inform the physician about the molecular changes underlying

the patient’s disease.

Genomic AlterationsThe genomic alterations driving tumor growth


FoundationOne® Report

Patient and ordering physician information

Targeted therapies and clinical trials that may be

beneficial based on genomic alterations

identified

Summary of genomic alterations identified

Swiss FoundationOne Report is based

on Swissmedic approvals



Swiss FoundationOne Report is based on Swissmedic approvals

Genomic Alterations

� Gene and Alteration

Role of the gene in cancer and

how alteration impacts gene

activity

� Frequency and Prognosis

� Potential Treatment Strategies

Therapeutic implications



Therapies

� Approved Indications of a drug

� Gene Association

Potential sensitivity or

resistance

� Supporting Data

Relevant clinical evidence

Swiss FoundationOne Report is based on Swissmedic approvals



Clinical Trials

Clinical Trials to consider listed

with phase, target, location and

NCT ID Information.


Phased Approach to Establish the FoundationOne®

Test in Switzerland

Today

from 2018 onward

Wet Lab Bioinformatic

Wet Lab

Bioinformatic


What to Consider for a Specific Set-up in CH?

• Workflow: the workflow was fitted into the Institute for Pathology

specifically.

• Equipment: the complete lab equipment was mirrored to FMI

Cambridge to ensure the same high quality standard.

• FTEs: lean university setting � 6 FTEs for the start.

• Validation & quality management: the quality management has the

high standard of FMI, but has to fit in the USZ overall management

system.

• Data protection & privacy: special forms and rules have to be

fullfilled according the USZ standards and Swiss Human Research Act.

• SAKK Collaboration with the Swiss Group for Clinical Cancer

Research (SAKK).


USZ Laboratory Operational End of 2017

RNA Prep Lab Pre-PCR Lab Post-PCR Lab Sequencing Lab

Sample

AccessioningIT Office

Meeting

RoomOffice Office

• 200 sqm new lab facility

• Lab layout follows comprehensive genomic profiling

workflow.

• Additional space for sample accessioning, IT and storage.

• The facility is embedded in the Biotechnopark Schlieren,

together with e.g. USZ Departments Oncology & Nuclear

Medicine, Roche Oncology Research, Molecular Partners.


OUR EXPERIENCE SO FAR

Patient 1, 29y/m - Adenocarcinoma



� Moderately differentiated adenocarcinoma

of the ascending colon (since 05/2015) pT3,

pN1b (3/70), G2

� No microsatellite instability (MSS)

� No NRAS, KRAS, BRAF mutation

� No APC, MUTHY mutation

DiagnosisRelevant information

Treatment statusAt presentation

Patient profile

� Laparoscopic-assisted colectomy and

ileorectal anastomosis 06/2015

� Adjuvant chemotherapy with FOLFOX (12

doses) 08/2015 – 01/2016

� Complete remission

� No radiological signs for tumor recurrence

(date of last visit: 7-SEP-2017 )

� 29-year-old male

� 2-year history of adenocarcinoma

of the ascending colon

� Suspected serrated polyposis

syndrome

� Pain in the right lower quadrant

� Weight loss of 5 kg within 6 months


Patient 1, 29y/m - AdenocarcinomaFoundationOne® Report - Cover


Patient 1, 29y/m - AdenocarcinomaInformation regarding Pharm Products and Clin Trials



FoundationOne ® analysis and subsequent treatment

FoundationOne Analysis

� Identification of POLE mutation (p.V411L),

high tumor mutational burden of

139 Muts/Mb, a microsatellite-stable tumor

and a PIK3CA mutation (p.T1025A).

� Molecular Tumorboard of 30-MAR-2017

• Human genetic advice recommended.

• Possible response to immune checkpoint-

inhibition (TMB).

• Discuss inclusion in SAKK 41/13 study

(ASS to prevent relapse).

Subsequent Treatment

� No immediate treatment consequences.

� However, patient was referred for germline

testing to the Institute of Medical Genetics,

UZH.

� Germ line test results are pending.


OUR EXPERIENCE SO FAR

Patient 2, 48y/m - Rectal carcinoma and hepatic metastasis


Patient 2, 48y/m - Rectal Carcinoma

DiagnosisRelevant information

Treatment status

At presentation

Patient profile

� APC / MUTYH, KRAS negative rectal

carcinoma with metachronous hepatic

metastasis

� Open low anterior rectal resection with total

mesorectal excision descendorectostomy,

lymphadenectomy of iliac lymph nodes and

protective ileostomy

� 2 Stage Hepatectomie (ALPPS 1 and 2)

� Systemic Therapy of FOLFIRI / Cetuximab

(stable disease)

� 48 year old male

� 3 year history of KRAS / BRAF /

NRAS-wildtype rectal carcinoma

and metachronous hepatic

metastasis

� Intermittent pain in the left

hypogastric region

� Tendency towards constipation


FoundationOne ® analysis and subsequent treatment

FoundationOne Analysis

� LF 2017.1 (B 2016.45546, Block 8, Foundation

One): 03/2017

� ATM p.R2832C

� KRAS p.Q61H

� APC p.R232*

� Sox9 R257fs*39

� TP53 R273C

� KRAS mutation

� ATM mutation

Subsequent Treatment

� No immediate treatment consequences

� Patient remains in complete remission, last

control 16-AUG-2017

� Possible Treatment Options� ATM mutation possibly sensitive for

PARP-inhibition (Olaparib)

� KRAS-mutation as a resistance

mechanism to EGFR-inhibition

(Cetuximab)


Thank you very much

10-martinzoche-expusz-fmi journ e seq-gfco 11102017xe9e%20ngs%2011%20... · martin zoche, gfco, oct...

Documents