cancer research uk stratified medicine programme rowena sharpe, phd head of precision medicine
TRANSCRIPT
CANCER RESEARCH UKSTRATIFIED MEDICINE PROGRAMME
ROWENA SHARPE, PhDHEAD 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
4
• 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
The Cancer Research UK Network
5
Cancer Research UK’s AmbitionOver 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.
We intend to achieve our ambition through a substantial increase in research spend in the following areas
Early diagnosis research
Basic understanding
of cancer
Cancer prevention
Therapeutic innovation
Precision medicine
Cancers of substantial
unmet need
To help deliver these priorities, we will:
Invest in our translational
network
Encourage collaborative approaches
Develop the best researchers
Launch new funding schemes
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
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
TSB grantees,
Additional partners,
£1.4m
£5.5 M
£5.6 M
£5.6 M
Service delivery
component
Research infrastructure
Central data repository (ECRiC)
The CRUK Stratified Medicine Programme was Designed to Demonstrate how
Cancer Gene Testing can be done on a Large Scale
Stratified Medicine Programme
Cardiff
CardiffUniversity
Hospital of Wale
s
Morriston
Singleton
Royal Gwen
t
Velindre
ManchesterThe
Christie
Wythenshawe
Salford
Royal
Pennine Acute
Glasgow
Royal Infir
mary
Western Infirmary
Southern Gene
ral
Golden
Jubilee
Gartnavel
Victoria
Infirmary
Stobhill
Hospital
Birmingham
BirminghamUniversity
Hospital
City
Edinburgh Western
General
Royal Infirmary
Cambridge
Addenbrooke's
Papworth
RMH
RMH
Marsden
Royal Brompton
Leeds
St. James's
General Infirmary
Technology HubsClinical HubsFeeder Hospitals
Infrastructure versus population density
The Programme was Delivered Through 3 Technology Hubs, 8 Clinical
Hubs and 26 Feeder Hospitals
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
A Range of Markers was Tested for Across Six Tumour Types
Colorectal Lung Breast Prostate Ovarian Melanoma
BRAF
KRAS
NRAS
PIK3CA
TP53
EML4 ALK
BRAF
EGFR
KRAS
DDR2
BRAF
TP53
PIK3CA
PTEN
BRAF
TMPRSS2-ERG
PTEN
BRAF
TP53
PTEN
BRAF
KIT
NRAS
PIK3CA
A Range of Markers was Tested for Across Six Tumour Types
Colorectal Lung Breast Prostate Ovarian Melanoma
BRAF
KRAS
NRAS
PIK3CA
TP53
EML4 ALK
BRAF
EGFR
KRAS
DDR2
BRAF
TP53
PIK3CA
PTEN
BRAF
TMPRSS2-ERG
PTEN
BRAF
TP53
PTEN
BRAF
KIT
NRAS
PIK3CA
CRUK Stratified Medicine Programme - Initial FindingsLung
EGFR mutation onlyKRAS mutation onlyBRAF mutation onlyALK rearrangement onlyEGFR + ALKEGFR + KRASFailed all gene testsWild-typeDDR2 mutation onlyKRAS + BRAFBRAF + ALKBRAF + DDR2DDR2 + 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% CONSENTNEED TO ESTABLISH ROUTINE CONSENT FOR RESEARCH USING TISSUE AND DATA
CRITICAL ROLE OF PATHOLOGY DEPARTMENT IN MANAGING TISSUE SAMPLESESTABLISH STANDARDS FOR SAMPLE HANDLING, PREPARATION AND PROCESSING
IMPACT OF MASS TESTING IN TECHNOLOGY HUBSACHIEVING CLINICALLY RELEVANT TURNAROUND TIMES
VALUE OF QA SYSTEMOPERATIONAL DELIVERY OF A STRATIFIED MEDICINE APPROACH
COMPLEXITIES OF NHS ITAUTOMATED 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?
Diagnostic biopsy
Generic consent
NHS Treatment
Consent for study
NHS Treatment
Recruit to drug 1
Recruit to drug 2
Recruit to drug 3
Recruit to drug n
EGFR
e.g. BRAF
Recruit if positive
NHS single gene test
Single gene test for study
e.g. NGSPanel test
If test negative
Collaborative pre-screening
SMP2: An Alternative Approach
•Shared cost•Quicker•Easier for patients•Fewer rebiopsies•Includes rare mutations
Current pathway
To Date: • Combined investment >£20M by current funding partners• Up to 14 AZ/Pfizer drugs
CRUK Stratified Medicine Programme 2 (SMP2) – A Collaborative Flexible Model
Biomarker etcDrug etc
Biomarker A :Drug A
Biomarker B :Drug B
Biomarker C :Drug C
Biomarker D :Drug D
Biomarker E:Drug E
Biomarker F :Drug F
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
• 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
Pre-screening MATRIX Lung Study
– 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
Summary
