Acknowledgements: The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK. Support is also provided by the Experimental Cancer Medicine Centre (programme grant) (to The ICR) and the National Institute for Health Research Biomedical Research Centre (jointly awarded to the RM NHS Foundation Trust and The ICR.

An introduction to the Drug Development Unit of The Royal Marsden NHS Foundation Trust &

The Institute of Cancer Research, UK

Acknowledgements: The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK. Support is also provided by the Experimental Cancer Medicine Centre (programme grant to the ICR) and the National Institute for Health Research Biomedical Research Centre (jointly awarded to The Royal Marsden NHS Foundation Trust and the ICR).

Celebrating 10 Years of the Drug Development Unit

2011 Rated “Outstanding” by the Experimental

Cancer Medicine Centre Network The FDA approved Abiraterone for sale under

the trade name Zytiga. Prof. Johann de Bono received prestigious

ESMO Award.

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Figure 1

Graph showing the number of trials facilitated by the Drug Development unit from 2005 to 2015. With 27 trials in 2005 and 47 in 2015, The Drug Development Unit has seen a steady increase in the number of open trials over the past 10 years. The types of drugs used in the trials have also changed. In 2005, there was a focus on single agent drugs, specifically inhibitors. However, recently, there has been an increase in the number of trials using combination therapies. There has also been a rise in the variety of trials undertaken by DDU; these include the use of immunotherapies, monoclonal antibodies, and alkylating agents.

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Graph showing the number of patients recruited onto trials facilitated by the Drug Development Unit from 2005 to 2015. The sharp increase seen in 2009 and 2010 corresponds to the large number of Merck trials run by the unit. Merck trials are reputed to be particularly fast recruiting.

2012 Recipient of the Team Science Award from the American Association for Cancer Research (AACR). This was the first time that the award has ever been won by a team from outside the USA. The AACR said its decision was based on “the tremendous impact this team has had in preclinical and clinical studies of cancer therapeutics.”

2016 Patient Satisfaction Survey gave Oak ward and Oak Day Unit a 5 star score rating, with 100% of all patients reviewed stating that they were likely to recommend us to family and friends.

2010 A Phase III trial reported that abiraterone could extend survival from 10.9 months to 14.8 months compared to a placebo, in men with late stage prostate cancer.

2017 Plans are being considered to relocate the

Unit to a new building to support the development of DDU’s infrastructure.

2005 The Drug Development Unit opens

with Prof Stan Kaye as the Director of DDU

2005 Total members of staff: 40

3 Consultants; 7 Clinical Staff ; 1 Clinical Trial Manager; 20 Research Nurses;

5 Trial management Staff; 4 Support Staff

2010Total members of staff: 77

4 Consultants; 12 Clinical Fellows; 20 Research Nurses; 1 Radiology Fellow;

1 Clinical Trial Manager; 2 Regulatory Officer; 1 Compliance Manager;

19 Trial Management Staff; 14 Support Staff; 1 Laboratory Staff;

2 Pharmacy Staff

2015 Total members of staff: 96

5 Consultants; 1 Radiology Consultant; 12 Clinical Fellows; 1 Radiology Fellow;

27 Research Nurses; 1 Head of Operations; 1 Administrator;

2 Regulatory Officers; 1 Compliance Manager; 1 Finance

Coordinator; 19 Trial Management Staff; 14 Support Staff; 3 Pharmacy Staff;

2 Laboratory Staff.

1 Head of IIT; 5 IIT Trial Management Staff.

2005 A number of drugs designed and developed in ICR were moved to Phase I trials in DDU. ICR developed on average two drug development candidates per year.

Snapshots of primary tumour sites treated in 2005 and 2015

Work of the Unit during the last 10 years

Timeline of DDU Structure and Achievements

2013 Establishment of the Investigator Initiated

Trials team (IIT) to sponsor, design and execute biomarker driven and stratified

academic studies.

Total members of IIT staff: 3 1 Head of IIT; 2 Trial Management Staff

Figure 3

Graph showing the primary tumour sites of patients treated by DDU, comparing the metrics between 2005 and 2015.

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2013 Received CRUK translational Research Award at the NCRI conference.

The aim of the Drug Development Unit is to seamlessly integrate preclinical drug discovery, proof-of-principle phase I trials and tumour-specific evaluation of novel agents.

Priorities of DDU are:

To maintain very highlevels of patient safety atall times.

To take forward rationallydesigned drugsdiscovered specifically atthe ICR.

To explore first-in-manstudies and first-in-mancombinations of drugs.

To develop drugs that arestratified and personalisedto patients in need.

To test novel therapieswhich would otherwise nottransition to next stages.

Aims and Principles

2006 In conjunction with The Royal Marsden NHS Foundation Trust, the ICR tested a promising new prostate cancer drug called Abiraterone, which it discovered and developed.

2012 Appointment of Prof Johann de Bono

as the Director of DDU

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The Drug Development Unit (DDU) was founded in February 2005 as a dedicated Phase I oncology clinical trial centre, designed and established through collaboration between Scientists & Clinicians at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.

DDU has grown from strength to strength since its inception with the support of researchers across multidisciplinary teams; our funders; and most important of all, our patients who trusted in the Unit. DDU is one of the leading clinical centres in the world providing novel drugs to over 300 patients within phase I trials each year & conducting about 45 Phase I clinical trials at any given time.

The success of DDU is built on its collaborative partnership between laboratory and clinical the modern drug development process.

DDU 2005

teams, a conduit that is critical to

DDU 2016

2015 BBC’s Panorama team was given unprecedented access to trials and ongoing research at the ICR and The Royal Marsden. The resulting episode, Can You Cure My Cancer?, was aired on BBC 1.

2014 DDU Fellows received Merit Awards at AACR,

ASCO and ESMO Conferences. Study setup of ComPAKT, by IIT, is the fastest

study to be set up as part of the alliance.

Acknowledgements: The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK. Support is also provided by the Experimental Cancer Medicine Centre (programme grant to the ICR) and the National Institute for Health Research Biomedical Research Centre (jointly awarded to The Royal Marsden NHS Foundation Trust and the ICR).

Celebrating 10 Years of the Drug Development Unit

The Drug Development Unit is committed to the early and optimal development of anti-cancer drugs which are novel and rationally designed to maximise the likelihood of patient benefit by strategically targeting molecular abnormalities and key cellular switches hijacked by cancer cells.

Selective & targeted treatments

BRCA, PTEN, PI3KCA, AKT, FRα, P53, ARID A1, BRAF, KRAS or NRAS, HER2, defective DNA repair genes, Mismatch repair genes

Fast tracking the development of anti-

cancer drugs designed and synthesised at ICR

to maximise their potential towards the care of cancer

patients.

Conducting biomarker-driven early clinical

trials focused on defining tolerability, proof of

mechanism and proof of concept.

Conducting early-phase clinical trials focused on

translating the understanding of cancer

biology to improve patient care as rapidly as

possible.

Effective Collaboration and Strategic Team

Science approach to enhance outcome of drug development

process.

@ the forefront of collaboration

Cancer Biomarker Team Pharmacodynamic Biomarker Team Drug Metabolism & Pharmacokinetic Team Cancer Biology & Cancer Evolution Team Multidisciplinary Clinical Units within RM

National & International Clinical Trial Centres CRUK and ECMC collaborative projects

Strategic alliances with Pharma Partners

DRUG DEVELOPMENT

UNIT

Phase-1 trials of ICR Drugs

Drug Mechanics Sponsor Abiraterone CYP17 inhibitor Janssen Biotech GDC-0941 PI3K inhibitor Genentech-Roche AUY922 HSP90 inhibitor Novartis CHR3996 HDAC inhibitor Chroma Therapeutics AT13148 ROCK inhibitor CRUK AZD5363 AKT inhibitor AstraZeneca Onx0801 α-Folate Receptor Onyx Pharmaceuticals BAL3833 PANRaf inhibitor Basilea Pharmaceutica CCT245737 CHK1 inhibitor CRUK

Licenced Drugs

Drug License Sponsor Abiraterone Zytega® Janssen Biotech Olaparib Lynparza® AstraZeneca RAD001 Afinitor® Novartis PDX101 Belinostat® Novartis

Number Of Drugs transitioned to next stages

Stages Number of Drugs

Common Disease Types

Phase II (single agent)

15 Lung, Liver, Breast, Prostate, H&N, NSCLC, Lymphoma, Renal, Sarcoma, Gynaecological, Pancreatic,

Phase II (combination) 22

Phase III (Single Agent)

17 Breast, Lung, Liver, Prostate, Gynaecological, NSCLC Phase III

(Combination) 13

Acknowledgements: The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK. Support is also provided by the Experimental Cancer Medicine Centre (programme grant to the ICR) and the National Institute for Health Research Biomedical Research Centre (jointly awarded to The Royal Marsden NHS Foundation Trust and the ICR).

Looking to the future: the next 10 years

Clinical Research Fellow posts with the Drug Development Unit (DDU) at The Royal Marsden Hospital & The Institute of Cancer Research, UK

An excellent opportunity for higher oncology trainees wishing to get experience of drug development and clinical trials.

DDU is a world-leading Phase I oncology trials unit evaluating a broad range of novel anti-cancer strategies (running >40 actively recruiting early phase trials, including first-in human).

Clinical research fellows gain extensive clinical experience of emerging novel anti-cancer strategies including targeted agents and combinations, immuno-oncology combinations, epigenetic and cell therapies.

In depth training of toxicity management, clinical trial conduct from conception to archival, protocol development, trial set-up, data analysis and presentation of findings.

The post includes interaction with industry partners as well as collaboration with laboratory scientists.

Contact: Juanita.Lopez@icr.ac.uk - Consultant Medical Oncologist

Acknowledgements: The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK. Support is also provided by the Experimental Cancer Medicine Centre (programme grant) (to The ICR) and the National Institute for Health Research Biomedical Research Centre (jointly awarded to the RM NHS Foundation Trust and The ICR.

DDU Clinical Fellows : Training a generation of Early Phase Trialists

CANADAMaxime Chenard-Poirier

Michael OngAlan Smith

AUSTRALIACraig CardenSamuel Harris

Chooi LeeBrent O'Carrigan

Shahneen SandhuTom Van Hagen

INDIANikhil Oommen Oomen

BRAZILAndre Brunetto

Alvaro Ingles RussoJoao Lima

Mariane Sousa Fontes

SPAINJorge Barriuso

Montserrat Blanco CodesidoMarta CapelanJesus Corral

Maria de Miguel LukenSophia FrentzasBegona Jimenez

David Lorente EstellasJoaquin Mateo Valderrama

Victor MorenoDavid OlmosRaquel Perez

Desam Roda-PerezLaura Vidal

FRANCE ITALYDiletta BianchiniAndrea Biondo

Gennaro DanieleElisa FontanaElisa Gallerani

Michela GuardisconeElena GuenaCristina MigaliMartina PuglisiKarim Rihawi

Leonardo TraniAndrea Zivi

Phillipe CassierChristophe MassardSophie Postel-Vinay

IRELANDScheryll Alken

Niamh ColemanDearbhaille Collins

GERMANYTobias Hendrik Arkenau

IRANSaeed Raafi

POLANDJanusz Mezynski

ROMANIANina Tunariu

GREECENikolaos DiamantisVasilios KaravasilisVasiliki Michalarea

Christos MikropoulosDionysios Papadatos-Pastos

USALiz Ye Han

MALAYSIAJoo Ern AngPeter Fong

SINGAPOREJoline Lim

Matthew NgRaghav Sundar

Daniel TanMabel Wong

NEW ZEALANDDean HARRISRajiv KUMAR

PAKISTANSalma AlamAwais Jalil

DENMARKJoanna Pedersen Vitfell

NETHERLANDSMartijn Lolkema

SCOTLAND (UK)Caroline Michie

Alison Reid

NORTHERN IRELAND (UK)Krurum Hayat Khan

SWITZERLANDAurelius Omlin

WALES (UK)Robert Jones

MALTAGert Attard

UNITED KINGDOMRoshan Agarwal

Richard BairdSuzie BanerjeeClare BarlowBristi Basu

Charlotte BensonRebecca BowenJessica Brown

Gary CookSaoirse DollyMartin ForsterMike GonzalezRobin JonesEmma Kipps

Rebecca KristeleitRohit Lal

Juanita LopezRhoda MolifeSimon Pacey

Geraldine PerkinsSanjay PopatDebs Sarker

Heather ShawRajesh SinhaJames Spicer

Naureen StarlingCharlie Swanton

David TanNicholas Turner

Axel WaltherTim Yap

Anna Mary Young

CYPRUSAnastasia Constantinidou

Acknowledgements: The Drug Development Unit of the Royal Marsden NHS Foundation Trust andThe Institute of Cancer Research is supported in part by a programme grant from Cancer ResearchUK. Support is also provided by the Experimental Cancer Medicine Centre (programme grant) (toThe ICR) and the National Institute for Health Research Biomedical Research Centre (jointlyawarded to the RM NHS Foundation Trust and The ICR