The Christie

Experimental Cancer Medicines Team

(ECMT)

Generic Slide Deck January 2015

Attendees from The Christie Name Position

Delivering Tomorrows Treatments Today

An Overview of the ECMT

***Experimental Medicine (MRC): “Investigation undertaken in humans, relating where appropriate to model

systems, to identify mechanisms of pathophysiology or disease, or to demonstrate proof-of-concept evidence of

the validity and importance of new discoveries or treatments.”

Leading Clinical Trials*

Leading Clinical

Research

Leading Experimental Medicine***

Regulatory Clinical

Pharmacology**

Biomarker qualification (Phase 0)

First in combination

First in Human

Virtual Biopsy

Precision Medicine

Real Time decision making

Preferred innovation

partner Training

*with investigational medicinal products=“CTIMP” in solid tumours

**Trials to characterise the PK conducted in parallel with the PhII/III programme

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“Phase 1” studies First in Human evaluation of a new cancer therapy in humans (FIH)

FIH first-in-class / biosimilar

First in Combination / Interaction Trial Approved agent + approved agent (s)

IMP + approved agent (s)

IMP + IMP

IMP + radiotherapy

Clinical Pharmacology Trials Pharmacokinetic focus

Bioavailability, food absorption study

Mass balance

liver/renal impairment,

DDIs

Pharmacodynamic focus

E.g. Imaging, tQT,

Biomarker and Target qualification / micro-dosing (Phase 0)

Cross cutting exploratory disease studies Adaptive / Molecular Stratification Trials

Multi-disease expansion arms

Why The Christie?

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Regulatory Clinical

Pharmacology

Biomarker qualification (Phase 0)

First in combination

First in Human

Leverage Key MCRC Differentiators

14,000 new patients

per annum in an

internationally known

centre

6x 24h dedicated

research beds

Biomarker Centre

on Campus -Investigational Procedures Unit

-Biofluid biomarkers: CRUK MI

-Molecular Pathology: Integrated

Pathology Suite & biobank

-Imaging biomarkers: WMIC

Research active disease

groups in integrated

clinical research facility

Clinical Trials which demand -rapid accrual

-disease specificity

-in and out-patient flexibility

-biomarker intensive

Why The ECMT?

5

Our ECMT “price promise” differentiators

Experience 175 CTIMP’s since 2007

XIAPi (SMI, ASO)

BH3 mimetic (SMI, ASO)

Survivin (ASO)

Chemotherapeutics

(Next generation)

PARPi

ATRi

HSPi

Avastin DDIs

VEGF trap

VEGFR-2mTORC1/2i

AKTi

MEKi

PI3Ki

EGFR DDIs, SMI, mAbs, pan-

EGFi

rhGH

IGF-1Ri (mAB)

HDACi

ALKi

MGMTi

Pemetrexed DDIs

Anti-Src & Abl TKIs

c-meti/Eph

FAKi

Ref: Cell 144:646-674;2011

Radiolabelled drugs

e.g. EGFRi, survivin antisense

Proteasome i

Radiolabelled anti-CD20 Ab

Ab-drug conjugates e.g. to CD30

Thromobopoietin fusion protein

Collaborative Mindset Awards and testimonials • “Thanks for being such a brilliant team”

(Pharma trial, Oct 2014)

• “[The Christie is] the highest recruiting site so far”

(Pharma/CRO trial, Sept 2014)

• “I have never before had such a proactive and

knowledgeable data manager” (Aug 2014)

• The Christie Staff Awards ‘Leading Cancer Care’

Highly Commended, (Dec 2013)

• European Society for Medical Oncology Award for

contribution to the fellowship programme (Sep 2013) Principle Investigators with

formal clin pharmacology

accreditation Each study has named SPOC to face sponsor=your extended team

Dedicated Investigator Time

•Safety review meetings

•Protocol review

•Publications review

•Adapting strategy

Your named investigator=your team physician

Delivery •Mean time from protocol receipt to

FSI= 93 days (n=10 ; range 74-144d)

•Mean time from contract to R&D

approval=2 days (n=10;; range 1-4d)

•Mean data entry time=2 days

•Every Phase 1 study achieves the

NIHR 70d set up (VRA to FSI) since

2013 (n=10)

•High level of clean data/low numbers

of unresolved data queries

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Capacity & Facilities CAPACITY

• Local population 3.2 million residents

• 30% patients from outside locality

• All major tumour types

• CRUK ‘major centre’

• One of six academic health science centres

(MAHSC, 2013)

• Ranked 1st in the UK for cancer research

(Research Assessment Exercise, RAE)

• Part of the Northern Academic Science cluster

FACILITIES

• Dedicated Early Phase Clinical Trials Unit

• 10 examination rooms, 31 beds/treatment

chairs, 6 inpatient beds, 5 out-patient suites

• Processing laboratory, phlebotomy

• Administrative floor for short-term archiving,

monitoring, audits

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Patient Population

40,000 pts/y

14,000 New pts/y

>2,000 on trials

500* on Ph1 trials

* 2020 projected figure

Catchment population

•Greater Manchester: 3,5 m

•Regional referral, >8 m

We offer treatment for all tumour types

High rate of lung and mesothelioma

>100 clinical trials

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Patient Referral Pathways

PIS Consent Screening

Patients Allocation Meeting

C1D1 Subsequent cycles

New Patients clinics Assessment

General Ph1 discussion

Referrals from

•Christie

•Other Hospitals

Disease

Progression

Suitable

for Ph1 Unsuitable

for Ph1

Changing Trends in Phase I Methods

Earlier treatment

settings; new

endpoints

Molecular

challenges

Access to /

funding of novel

therapies

COMPLEX TRIALS

• Combination / multimodality

/ n=1 trials

• Prospective & serial

molecular testing (Western

cf. Asian population)

• Key Performance Indicators

(KPIs) e.g. data entry

COMPLEX PATIENTS

• Competitive recruitment &

limited slot availability

• Multiple consent processes

• Multiple research samples

• Compliance

• Patient-centred drug

development

Site Days to data entry (Av.)

1 21.0

2 2.6

3 5.1

4 6.3

5 10.5

6 6.2

Experimental Cancer

Medicine Team

Clinical Study Team Composition: Named members

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Core Treatment Unit

Core

nursing

staff

Clinical

Research

Nurses

Principal

Investigators

Clinical Trial

Coordinators

Clinical

Trial

Pharmacist

Healthcare

assistants

Laboratory

Technicians

Angela White (0.75)

Advanced

Nurse

Practitioners

& Clinical

Fellows

Secretary

Emma Dean (1.0)

Andrew Hughes (0.7)

Matthew Krebs (1.0)

Heather O’Driscoll (1.0)

Sukhy Thandi (1.0)

Carla Siswick* (1.0)

Claire Davies (1.0)

Hannah Gornall (1.0)

*Translational Science technician

Andrea Burgess (0.4)

Lorraine Turner (0.6)

Michelle Davies (1.0)

Debra Jowle (1.0)

Alison White (0.8)

Helen Shekelton (0.7)

Anisah Mehmood (1.0)

Julie Dewane

+2 Alkesh Patel

n=3 n=1

The Christie Disease Groups: Inter-dependency

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Research active Disease Teams co-located in a common Clinical Research Facility

Oak Road

Treatment Centre ECMT can support

•MSc Experimental Cancer Medicine

•PhD Clinical Fellow placement

•Trial referrals

•Annual funding call for ISS’s

•Expertise in protocol review

•Prototyping clinical data acquisition tools

•Publications as co-investigators

DAT can support •Patient referrals

•Trial referrals

•Disease specific tox interpretation

Leading Clinical Research

Leading Clinical Trials

Leading Clinical

Research

Leading Experimental

Medicine*

Regulatory Clinical

Pharmacology

Biomarker qualification (Phase 0)

First in combination

First in Human

Liquid Biopsy

Precision Medicine

Real Time decision making

Preferred innovation

partner Training

Our 4 Clinical Research Themes

Top 3 EU Experimental

Cancer Medicine Team

Liquid

Biopsy

Precision

Medicine

Real Time

data

enabled

decision

making

Preferred

Innovation

Partner*

Training

Beacon

WE DISCOVER Our research agenda

WE CARE Our trials agenda

WE TEACH Our education agenda

-To increase

#patients with options

-To increase

#novel therapies

-To increase

#clinical trials

-

-The “Go To”

training centre

-To increase

#world class staff

-To increase

#patient referrals

-To move to earlier

lines of therapy

-To increase

#responding patients

-To increase

#rational combinations

-To adapt the trial

-To decrease

#data queries

-To decrease

data entry time

13 * with best of breed in sector

Liquid Biopsy Precision Medicine

•Embracing CRUK MI, ICS Centre Personalised Therapy & Catapult research themes

•A “must have” for any world class experimental therapeutics unit

Protocols: Potential for hospital-wide collection of samples from patients (i) on standard of care or trial pathway (ii) super-responders in clinical

trial (iii) super-resistance in clinical trial

Tissue: Operational linkage with Investigational Procedures Unit and MCRC Biobank

Biofluids: Operational linkage with Centre Biomarker sciences, “omics” groups and Manchester Centre Genomic Medicine

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Real Time data enabled decision making (iDECIDE)

•Aligned with CRUK MI Centre Biomarker Sciences research agenda

•Will become “must have” for any world class experimental therapeutics unit

Real Time data entry and cleaning to Sponsor: eSource

Visualisation of biomarker data alongside other clinical trial data

Smartphone technology to inform and be informed by patients

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Preferred Innovation Partner working

•Aligned to CRUK Major centre and The Christie “increased interaction” agendas.

•A “must have” in an era of basket/bucket/molecularly matched “Phase1’s”

Academic Groups: Initial focus on -NorthWest & “northern hub” centres

ECMC centres

-CRUK Major centres:

-CRUK-NCRN

-Eurocan/IARC centres

Pharma: Initial focus on -“Phase 1” FIHuman & FICombination trials

-Regulatory Clinical Pharmacology trials

-”Phase 0” biomarker and human target qualification trials

CRO: Initial focus on -“Phase 1” FIHuman & FICombination trials

-Regulatory Clinical Pharmacology trials

-”Phase 0” biomarker and human target qualification trials

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Training Beacon

•Educating on the national/international impact of experimental therapeutics today

•Developing the cancer leaders and collaborators of tomorrow

Clinical Fellows Training Scheme -CRUK Experimental Cancer Medicine clinical fellowship (MSc)

CRUK-AZ Clinical Pharmacology programme (PhD) -Participation in society schemes eg ESMO

-oncology trainees form medical oncology training curriculum

All ECMT staff have -Staff development programme for clinical research training,

experimental cancer medicine and transferrable skills

-career ladders

MSc Experimental Cancer Medicine -1y full time training

-available to all qualified clinical research staff -taught modules available ad hoc to staff

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Division of Research @ The Christie

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R&D Division –

Key tasks /

activity areas

Clinical trial

patient

management

Tissue bankClinical trials

Co-ordination

Core R&D /

Division

services

Recruitment of

patients to trials

Coordination of local

trial set ups

Coordination of

National and

International trials

Collection and storage

of tissue samples for

academic and

commercial use

Management of R&D

database

Research Governance

& Monitoring

DH and Division

performance reporting

R&D Core Services

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R&D Office

• Trial set-up

• Trial amendments

• Research governance

• Contract approval (wording)/

facilitation

• Partnerships

• Sponsor oversight

• Research strategy

• Archiving

• Quality

Business Planning

• Support costing and negotiation

off all trials

• Contract approval (finances)

• Invoicing for trials

• R&D costing system

• Grant management

• Financial advice

• Assess and report on the full

resource impact of research

trials at the Christie

• Information systems

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Facilities Tour