1. Cancer Research UK STRATIFIED MEDICINE PROGRAMME
Rowena Sharpe, PhD
Head of precision medicine

2. A brief introduction to
Cancer Research UK

3. 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

4. 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

5. 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.

6. We intend to achieve our ambition through a substantial increase in research spend in the following areas
Early diagnosis research
Basic understanding of cancer
Therapeutic innovation
Cancers of substantial unmet need
Cancer prevention
Precision medicine
To help deliver these priorities, we will:
Launch new funding schemes
Invest in our translational network
Encourage collaborative approaches
Develop the best researchers

7. CRUK Stratified Medicine 1

8. CRUK Stratified Medicine Programme (Phase 1) – In a Nutshell
The phase 1 component ( ) 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

9. 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
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
£5.5 M
£5.6 M
£5.6 M

10. Central data repository (ECRiC)
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

11. Stratified Medicine Programme
The Programme was Delivered Through 3 Technology Hubs, 8 Clinical Hubs and 26 Feeder Hospitals
Stratified Medicine Programme
Cardiff
University Hospital of Wales
Morriston
Singleton
Royal Gwent
Velindre
Manchester
The Christie
Wythenshawe
Salford Royal
Pennine Acute
Glasgow
Royal Infirmary
Western Infirmary
Southern General
Golden Jubilee
Gartnavel
Victoria Infirmary
Stobhill Hospital
Birmingham
University Hospital
City
Edinburgh
Western General
Cambridge
Addenbrooke's
Papworth
RMH
Marsden
Royal Brompton
Leeds
St. James's
General Infirmary
Infrastructure versus population density
Technology Hubs
Clinical Hubs
Feeder Hospitals

12. CR UK Stratified Medicine Programme – Key Metrics
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

13. A Range of Markers was Tested for Across Six Tumour Types
Colorectal
Lung
Breast
Prostate
Ovarian
Melanoma
BRAF
KRAS
NRAS
PIK3CA
TP53
EML4 ALK
EGFR
DDR2
PTEN
TMPRSS2-ERG
KIT

14. A Range of Markers was Tested for Across Six Tumour Types
Colorectal
Lung
Breast
Prostate
Ovarian
Melanoma
BRAF
KRAS
NRAS
PIK3CA
TP53
EML4 ALK
EGFR
DDR2
PTEN
TMPRSS2-ERG
KIT

15. CRUK Stratified Medicine Programme - Initial Findings Lung
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%).

16. 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

17. CRUK Stratified Medicine 2

18. CRUK Stratified Medicine Programme 2 (SMP2)
A TWO PART SOLUTION TO ADDRESS THE KEY OPERATIONAL CHALLENGES OF DELIVERING STRATIFIED MEDICINE:
Large volume molecular pre-screening.
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

19. Why Lung?

21. Single gene test for study
SMP2: An Alternative Approach
Current pathway
NHS single gene test
NHS Treatment
Single gene test for study
Consent for study
Diagnostic biopsy
Recruit if positive
EGFR
If test negative
e.g. BRAF
Shared cost
Quicker
Easier for patients
Fewer rebiopsies
Includes rare mutations
NHS Treatment
Recruit to drug 1
Recruit to drug 2
Recruit to drug 3
Collaborative
pre-screening
Recruit to drug n
Generic consent
Panel test
e.g. NGS

22. 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

23. Pre-screening NGS sequencing MATRIX Lung Study
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
NGS sequencing
MATRIX Lung Study
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
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

24. 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

25. The end Rowena Sharpe Angel Building 407 St. John Street London
EC1V 4AD