CANCER RESEARCH UK STRATIFIED MEDICINE PROGRAMME 2 CHRIS BAKER PhD BUSINESS DEVELOPMENT MANAGER STRATEGIC PARTNERSHIPS

CRUK STRATIFIED

MEDICINE 1- THE PAST

CRUK Stratified Medicine Programme (Phase 1) – In a Nutshell

• Collaborative initiative to undertake large volume genetic testing within the UK

• Test approximately 9000 patients across the UK over a 2 year programme (2011-2013)

• 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

CRUK Stratified Medicine Programme (Phase 1) – Key Metrics

Poor quality Sample

Increased test failures

Increased test repeats

Increased TAT

Decreased mutation

rate

Artefacts

Sample Quality is Critical

CRUK Stratified Medicine Programme (Phase 1) – Key Learning

CRUK STRATIFIED

MEDICINE 2

5 Key Approaches & the Stratified Medicine Programme 2

• Build our understanding of cancer

• Facilitate a major shift in early diagnosis research

• Tackle cancers with substantial unmet need

• Accelerate the translation of research

• Develop the cancer research leaders of tomorrow

CRUK Research Strategy (May 2014)

CRUK Stratified Medicine Programme 2 (SMP2) – Tackle cancers with substantial unmet need

Routine Therapeutic Intervention – everyone gets the same

CRUK Stratified Medicine Programme 2 (SMP2) – Accelerate the translation of research

A few patients selected for a specific Biomarker:

e.g. EGFR / ALK

CRUK Stratified Medicine Programme 2 (SMP2) – Routine Stratified Therapy

Biomarker A : Drug A

Biomarker B : Drug B

Biomarker C : Drug C

Biomarker D : Drug D

CRUK Stratified Medicine Programme 2 (SMP2) – CRUK Stratified Therapy

“NATIONAL SCREENING TO NATIONAL TRIALS”

• A truly differentiated National stratified medicine programme

• Change the UK landscape for delivery of stratified medicine

• Large volume molecular pre-screening (build on SMP1)

• National Matrix Trial to deliver the right drugs to the right place for the right patient

• The programme is future proof: • amenable to new drugs

• amenable to new technologies

• potential for new indications and combination strategies

CRUK Stratified Medicine Programme 2 (SMP2)

• Combined investment >£20M by current funding partners • Up to 14 AZ/Pfizer drugs

CRUK Stratified Medicine Programme 2 (SMP2) – A Collaborative Model

Patients

Late stage metastatic lung

cancer

Non-resection samples

2000 patients per year

Pathology

Pathology standards

Sample handling

guidelines

Data

Streamline collection

Secure storage for research

use

Testing

Multiplexed solution to

develop over the course of

the programme

Clinically relevant

turnaround times

CRUK Stratified Medicine Programme 2 (SMP2) – Molecular Pre-Screening

• Extensive review chose as the panel provider

• Nextera Rapid Capture enrichment used for NGS panel

• Multiple types of genetic aberration: • Single Nucelotide Variants (SNV) • Insertions & deletions (Indel) • Copy number variations (CNV) • DNA rearrangements

• Genes for analysis can be revised

CRUK Stratified Medicine Programme 2 (SMP2) – Molecular Pre-Screening NGS Panel

• A national study open at all ECMCs • Each ECMC can act as a hub for surrounding hospitals

• One clinical trial protocol and regulatory submission • Diagnostic samples will be required to enable

molecular pre-screening prior to clinical trial entry • Repeat biopsy will be offered to patients at relapse • Biopsy will also be taken (where possible) post

therapy to compare molecular characterisation pre and post therapy

CRUK Stratified Medicine Programme 2 (SMP2) – The National Matrix Trial

• Chief Investigator: Gary Middleton

• Clinical Trial Unit: Birmingham

• Chair of the Trial Management Group: Sanjay Popat

CRUK Stratified Medicine Programme 2 (SMP2) – The National Matrix Trial Management

Clinical Hub for pre-screening Technology Hub

CRUK Stratified Medicine Programme 2 (SMP2) – Build from SMP1 Infrastructure

CRUK Stratified Medicine Programme 2 (SMP2) – Expand to National Structure

Clinical Hub for pre-screening Technology Hub ECMC - Clinical trial open

Biomarker Arm 1

Biomarker Arm 2 AZD4547 - FGFR

AZD2014 - mTORC

Palbociclib - CDK4/6

Crizotinib - ALK

Biomarker Arm 3

Biomarker Arm 4

Biomarker Arm 5

Biomarker Arm 7

Biomarker Arm 6

Biomarker Arm 14

Selumetinib + Docetaxol

Medi4376 - PDL1

Biomarker Arm 8

Biomarker Arm 12

Biomarker Arm 11

Biomarker Arm 13

Biomarker Arm 9

Biomarker Arm 10

Drug X.....

CRUK Stratified Medicine Programme 2 (SMP2) – Multiple Arms/Cohorts Based on Biomarker Selection

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Arm 1

Arm3

Arm n = .......

Arm 10

Arm 9

Arm 8

Arm 7

Arm 6

Arm 5

Arm 2

Arm 4

Clinical Centre 1

Clinical Centre 2

Clinical Centre 3

Clinical Centre 4

Clinical Centre n =......

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CRUK Stratified Medicine Programme 2 (SMP2) – All Centres have access to All Arms

• SMP2 will change the way we develop stratified medicines within the UK and provide greater options for patients with lung cancer

• The programme will be a National effort across the entire CRUK ECMC network and beyond

• A model utilising shared pre-screening provides benefits for patients, Sponsors and pharmaceutical companies

CRUK Stratified Medicine Programme 2 (SMP2) – Summary

THE END

Chris Baker Angel Building 407 St. John Street London EC1V 4AD

+44 (0)20 3469 6305 cbaker@cancertechnology.com