CANCER RESEARCH UK
STRATIFIED MEDICINE PROGRAMME
ROWENA SHARPE, PhD
HEAD OF PRECISION MEDICINE
A brief introduction to
Cancer Research UK
Cancer Research UK (CRUK)
•
Largest fundraising medical research charity
in the world (no government support)
•
Largest funder of cancer research in Europe
•
Spent £392m on research in 2014/15
•
Support over 5,000 scientists, clinicians and
nurses
•
75% of the UK’s cancer clinical trial patients
are recruited onto CRUK supported trials
The Cancer Research UK Network
• 18 Experimental Cancer Medicine
Centres (ECMCs)
• 15 Centres
• 7 Clinical Trials Units
• 5 core-funded institutes
• 4 Cancer Imaging Centres
+ CRUK Centre for Drug Development
+ CRT Discovery Laboratories
4
Cancer Research UK’s Ambition
Over the last 40 years, cancer survival in the UK has doubled. In the 1970s just a quarter
of people survived. Today that figure is half.
Our ambition is to accelerate progress an see three-quarters of patients surviving the
disease within the next 20 years.
5
We intend to achieve our ambition through a substantial
increase in research spend in the following areas
Early
diagnosis
research
Basic
Therapeutic
understanding
innovation
of cancer
Cancers of
Cancer
Precision
substantial
prevention
medicine
unmet need
To help deliver these priorities, we will:
Launch new
funding
schemes
Invest in our
translational
network
Encourage
collaborative
approaches
Develop the
best researchers
CRUK
STRATIFIED
MEDICINE 1
CRUK Stratified Medicine Programme (Phase 1) – In a
Nutshell
 The phase 1 component (2011-2013) of the CRUK
Stratified Medicine Programme was a collaborative
initiative to undertake large volume genetic testing
within the UK
 Test approximately 9000 patients across the UK over
a 2 year programme
Stratified Medicine Pilot Programme was driven by CRUK but supported
by Pharma, the Government, Diagnostic and IT Companies
CR-UK, Pfizer and
AstraZeneca fund the
clinical and tech. hubs
Additional
partners,
£1.4m
£5.5 M
£5.6 M
TSB
grantees,
Technology Strategy Board
and grantees develop new
IT and panel tests
Department of Health Chief
Medical Officer & National
Health Service
Additional partners, Bristol
Myers Squibb and Roche
provide funding for
additional tests and Oracle
provide analytics platform
£5.6 M
The CRUK Stratified Medicine Programme was Designed to Demonstrate
how Cancer Gene Testing can be done on a Large Scale
Central data
repository (ECRiC)
Research
infrastructure
Service
delivery
component
The Programme was Delivered Through 3 Technology Hubs, 8 Clinical
Hubs and 26 Feeder Hospitals
Stratified Medicine Programme
Birmingham
Cardiff
Cardiff
University
Hospital of
Wales
Morriston
Manchester
Birmingham
Edinburgh
The Christie
Royal
Infirmary
University
Hospital
Western
General
Wythenshawe
Western
Infirmary
City
Royal
Infirmary
Salford
Singleton
Glasgow
Royal
Southern
General
Pennine
Acute
Golden
Jubilee
Royal Gwent
Gartnavel
Velindre
Victoria
Infirmary
Stobhill
Hospital
RMH
Cambridge
RMH
Addenbrooke's
Papworth
Leeds
Marsden
St. James's
Royal
Brompton
General
Infirmary
Infrastructure versus
population density
Technology Hubs
Clinical Hubs
Feeder Hospitals
CR UK Stratified Medicine Programme – Key Metrics
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Almost 40,000 gene tests
10,754 patients consented
9,010 samples sent for testing
26 feeder hospitals
8 clinical hubs
6 tumour types
3 technology hubs
1 network
A Range of Markers was Tested for Across Six Tumour
Types
Colorectal
Lung
Breast
Prostate
Ovarian
Melanoma
BRAF
EML4 ALK
BRAF
BRAF
BRAF
BRAF
KRAS
BRAF
TP53
TMPRSS2ERG
TP53
KIT
NRAS
EGFR
PIK3CA
PTEN
NRAS
PTEN
PIK3CA
KRAS
TP53
DDR2
PTEN
PIK3CA
A Range of Markers was Tested for Across Six Tumour
Types
Colorectal
Lung
Breast
Prostate
Ovarian
Melanoma
BRAF
EML4 ALK
BRAF
BRAF
BRAF
BRAF
KRAS
BRAF
TP53
TMPRSS2ERG
TP53
KIT
NRAS
EGFR
PIK3CA
PTEN
NRAS
PTEN
PIK3CA
KRAS
TP53
DDR2
PTEN
PIK3CA
CRUK Stratified Medicine Programme - Initial Findings
Lung
EGFR mutation only
KRAS mutation only
BRAF mutation only
ALK rearrangement only
EGFR + ALK
EGFR + KRAS
Failed all gene tests
Wild-type
DDR2 mutation only
KRAS + BRAF
BRAF + ALK
BRAF + DDR2
DDR2 + KRAS
• Of 1889 lung cancers, 35% had at least one abnormality
• Only 0.65% had more than one.
• KRAS was most often mutated (26%), followed by EGFR (8.3%), ALK
rearrangement (1.9%) and BRAF (1%).
Findings from the CRUK Programme
GENERAL ACCEPTABILITY TO PATIENTS: OVER 98% CONSENT
NEED TO ESTABLISH ROUTINE CONSENT FOR RESEARCH USING TISSUE AND DATA
CRITICAL ROLE OF PATHOLOGY DEPARTMENT IN MANAGING TISSUE SAMPLES
ESTABLISH STANDARDS FOR SAMPLE HANDLING, PREPARATION AND PROCESSING
IMPACT OF MASS TESTING IN TECHNOLOGY HUBS
ACHIEVING CLINICALLY RELEVANT TURNAROUND TIMES
VALUE OF QA SYSTEM
OPERATIONAL DELIVERY OF A STRATIFIED MEDICINE APPROACH
COMPLEXITIES OF NHS IT
AUTOMATED DATA EXTRACTION NOT YET RELIABLE
CRUK
STRATIFIED
MEDICINE 2
CRUK Stratified Medicine Programme 2 (SMP2)
A TWO PART SOLUTION TO ADDRESS THE KEY OPERATIONAL
CHALLENGES OF DELIVERING STRATIFIED MEDICINE:
1. Large volume molecular pre-screening.
2. National Matrix study to deliver the right drugs
to the right place for the right patient.
•
•
•
Paradigm shift in how the UK delivers precision medicine
Future proof: Ability to evolve
Initial focus on an area of clear unmet need: lung cancer,
one of CRUK’s strategic priorities
Why Lung?
SMP2: An Alternative Approach
Current pathway
NHS single
gene test
NHS
Treatment
Consent for
study
Diagnostic
biopsy
EGFR
Single gene
test for study
Recruit if
positive
If test
negative
e.g. BRAF
NHS Treatment
Recruit to drug 1
Recruit to drug 2
Recruit to drug 3
Collaborative
pre-screening
Generic
consent
Panel test
e.g. NGS
Recruit to drug n
•Shared cost
•Quicker
•Easier for
patients
•Fewer
rebiopsies
•Includes
rare
mutations
CRUK Stratified Medicine Programme 2 (SMP2)
– A Collaborative Flexible Model
To Date:
• Combined investment
>£20M by current
funding partners
• Up to 14 AZ/Pfizer drugs
Biomarker A :
Drug A
Biomarker B :
Drug B
Biomarker C :
Drug C
Biomarker D :
Drug D
Biomarker E:
Drug E
Biomarker F :
Drug F
Biomarker etc
Drug etc
Pre-screening
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•
•
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NGS sequencing
Currently upto 2000 NSCLC patients screened per year
Utilising DNA from routine FFPE biopsies
28 gene multiplexed NGS panel; detects mutations,
deletions, CNV and DNA rearrangement
National screening to national trial
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MATRIX Lung Study
Phase 2a signal finding study
8 drugs, 21 stratified arms to begin with
Sponsored by the University of Birmingham
CI Professor Gary Middleton,
Coordinated by Birmingham CRCTU
Centralised pharmacy & recruitment across 18 ECMCs
Rolling protocol, capable of incorporating new arms
Summary
– SMP2 will change the way we develop stratified medicines
within the UK and provide greater options for patients with
lung cancer.
– SMP2 is a highly collaborative & flexible model to allow for
clinical testing of drugs in many novel patient populations
– The programme is a robust National effort across the entire
CRUK ECMC network and beyond
– A model utilising shared pre-screening provides benefits for
patients, researchers and pharmaceutical companies
– Takes us another step along the pathway to true precision
medicine
THE END
Rowena Sharpe
Angel Building
407 St. John Street
London
EC1V 4AD
Rowena.sharpe@cancer.org.uk