An Introduction to the Drug Development Unit of the Royal Marsden NHS Foundation Trust & the Institute of Cancer Research, UK

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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 RM NHS Foundation Trust and The ICR. Celebrating 10 Years of the Drug Development Unit

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 DDU 2005 time. The success of DDU is built on its collaborative partnership between laboratory and clinical t eams, a conduit that is critical to the modern drug development process.

Aims and Timeline of DDU Structure and Work of the Unit during the Principles Achievements last 10 years

2005 Number of trials enrolling patients The aim of the Drug The Drug Development Unit opens Development Unit is to with Prof Stan Kaye as the Director of DDU per year 50 seamlessly integrate 2005 45 2005 A number of drugs designed and developed in ICR Total members of staff: 40 were moved to Phase I trials in DDU. ICR 40

preclinical drug discovery, 3 Consultants; 7 Clinical Staff ; developed on average two drug development 35 1 Clinical Trial Manager; 20 Research Nurses; candidates per year. 30 proof-of-principle phase I 5 Trial management Staff; 4 Support Staff 25 trials and tumour-specific 20 2006 15 In conjunction with The Royal Marsden NHS evaluation of novel agents. 10 Foundation Trust, the ICR tested a promising new Number ofNumber trials 5 prostate cancer drug called Abiraterone, which it discovered and developed. 0 Priorities of DDU are: 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Figure 1  To maintain very high 2010 2010 Total members of staff: 77 A Phase III trial reported that abiraterone could Graph showing the number of trials facilitated by the Drug Development unit from 2005 to levels of patient safety at 4 Consultants; 12 Clinical Fellows; extend survival from 10.9 months to 14.8 months 2015. With 27 trials in 2005 and 47 in 2015, The Drug Development Unit has seen a steady 20 Research Nurses; 1 Radiology Fellow; compared to a placebo, in men with late stage increase in the number of open trials over the past 10 years. The types of drugs used in the all times. 1 Clinical Trial Manager; 2 Regulatory Officer; prostate cancer. trials have also changed. In 2005, there was a focus on single agent drugs, specifically 1 Compliance Manager; inhibitors. However, recently, there has been an increase in the number of trials using  To take forward rationally 19 Trial Management Staff; combination therapies. There has also been a rise in the variety of trials undertaken by DDU; 14 Support Staff; 1 Laboratory Staff; 2011 these include the use of immunotherapies, monoclonal antibodies, and alkylating agents. designed drugs 2 Pharmacy Staff  Rated “Outstanding” by the Experimental Cancer Medicine Centre Network discovered specifically at  The FDA approved Abiraterone for sale under the trade name Zytiga. the ICR.  Prof. Johann de Bono received prestigious Number of patients enrolled ESMO Award.  To explore first-in-man per year 2012 300 studies and first-in-man 2012 Recipient of the Team Science Award from the 250 Appointment of Prof Johann de Bono American Association for Cancer Research

combinations of drugs. as the Director of DDU (AACR). This was the first time that the award has 200  To develop drugs that are ever been won by a team from outside the USA. The AACR said its decision was based on “the 150 2013 tremendous impact this team has had in preclinical Establishment of the Investigator Initiated stratified and personalised and clinical studies of cancer therapeutics.” Trials team (IIT) to sponsor, design and 100 to patients in need. execute biomarker driven and stratified academic studies. 2013 50  To test novel therapies Received CRUK translational Research Award at ofNumber patients 0 Total members of IIT staff: 3 the NCRI conference. 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 which would otherwise not 1 Head of IIT; 2 Trial Management Staff Figure 2 transition to next stages. 2014 Graph showing the number of patients recruited onto trials facilitated by the Drug  DDU Fellows received Merit Awards at AACR, Development Unit from 2005 to 2015. The sharp increase seen in 2009 and 2010 ASCO and ESMO Conferences. corresponds to the large number of Merck trials run by the unit. Merck trials are reputed to 2015  Study setup of ComPAKT, by IIT, is the fastest be particularly fast recruiting. Total members of staff: 96 study to be set up as part of the alliance. 5 Consultants; 1 Radiology Consultant; 12 Clinical Fellows; 1 Radiology Fellow; 27 Research Nurses; Snapshots of primary tumour sites 1 Head of Operations; 1 Administrator; 2015 2 Regulatory Officers; BBC’s Panorama team was given unprecedented treated in 2005 and 2015 1 Compliance Manager; 1 Finance access to trials and ongoing research at the ICR 60 Coordinator; 19 Trial Management Staff; and The Royal Marsden. The resulting episode, 14 Support Staff; 3 Pharmacy Staff; Can You Cure My Cancer?, was aired on BBC 1. 50 2 Laboratory Staff. 40 1 Head of IIT; 5 IIT Trial Management Staff. 2016 30 Patient Satisfaction Survey gave Oak ward and 2017 Oak Day Unit a 5 star score rating, with 100% of all 20 Plans are being considered to relocate the patients reviewed stating that they were likely to 10 Unit to a new building to support the recommend us to family and friends. development of DDU’s infrastructure.

Number ofNumber patients 0

DDU 2016 2005 2015 Figure 3

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

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.

Phase-1 trials of ICR Drugs Drug Mechanics Sponsor Fast tracking the Abiraterone CYP17 inhibitor Janssen Biotech development of anti- GDC-0941 PI3K inhibitor Genentech-Roche cancer drugs designed and synthesised at ICR AUY922 HSP90 inhibitor Novartis DRUG to maximise their potential CHR3996 HDAC inhibitor Chroma Therapeutics DEVELOPMENT towards the care of cancer AT13148 ROCK inhibitor CRUK UNIT patients. AZD5363 AKT inhibitor AstraZeneca Onx0801 α-Folate Receptor Onyx Pharmaceuticals BAL3833 PANRaf inhibitor Basilea Pharmaceutica CCT245737 CHK1 inhibitor CRUK Conducting early-phase clinical trials focused on translating the Licenced Drugs understanding of cancer biology to improve patient Drug License Sponsor care as rapidly as Abiraterone Zytega® Janssen Biotech possible. Olaparib Lynparza® AstraZeneca RAD001 Afinitor® Novartis Effective Collaboration and Strategic Team PDX101 Belinostat® Novartis Science approach to enhance outcome of Conducting biomarker- drug development driven early clinical Number Of Drugs transitioned to next stages process. trials focused on defining Stages Number Common Disease Types tolerability, proof of of Drugs mechanism and proof of Phase II Lung, Liver, Breast, Prostate, concept. 15 (single agent) H&N, NSCLC, Lymphoma, Phase II Renal, Sarcoma, 22 (combination) Gynaecological, Pancreatic, @ the forefront of collaboration Phase III 17 (Single Agent) Breast, Lung, Liver, Prostate, Cancer Biomarker Team Phase III 13 Gynaecological, NSCLC Pharmacodynamic Biomarker Team (Combination) Drug Metabolism & Pharmacokinetic Team Cancer Biology & Cancer Evolution Team Multidisciplinary Clinical Units within RM Selective & targeted treatments

National & International Clinical Trial Centres BRCA, PTEN, PI3KCA, AKT, FRα, P53, ARID A1, CRUK and ECMC collaborative projects BRAF, KRAS or NRAS, HER2, defective DNA repair genes, Mismatch repair genes Strategic alliances with Pharma Partners

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

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). 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: [email protected] - Consultant Medical Oncologist

UNITED KINGDOM Roshan Agarwal Juanita Lopez SCOTLAND (UK) Richard Baird Rhoda Molife Caroline Michie Suzie Banerjee Simon Pacey Alison Reid Clare Barlow Geraldine Perkins Bristi Basu Sanjay Popat Charlotte Benson Debs Sarker DENMARK Rebecca Bowen Heather Shaw Joanna Pedersen Vitfell Jessica Brown Rajesh Sinha Gary Cook James Spicer NORTHERN IRELAND (UK) Saoirse Dolly Naureen Starling Krurum Hayat Khan Martin Forster Charlie Swanton Mike Gonzalez David Tan Robin Jones Nicholas Turner IRELAND Emma Kipps Axel Walther Rebecca Kristeleit Tim Yap Scheryll Alken Rohit Lal Anna Mary Young Niamh Coleman Dearbhaille Collins CANADA Maxime Chenard-Poirier Michael Ong NETHERLANDS Alan Smith Martijn Lolkema POLAND Janusz Mezynski GERMANY Tobias Hendrik Arkenau WALES (UK) Robert Jones

USA Liz Ye Han IRAN Saeed Raafi FRANCE ITALY Phillipe Cassier Diletta Bianchini Andrea Biondo Christophe Massard ROMANIA Sophie Postel-Vinay Gennaro Daniele Elisa Fontana Nina Tunariu Elisa Gallerani PAKISTAN SPAIN Michela Guardiscone INDIA Elena Guena Salma Alam Jorge Barriuso Awais Jalil Nikhil Oommen Oomen Cristina Migali Montserrat Blanco Codesido Martina Puglisi Marta Capelan Karim Rihawi Jesus Corral Leonardo Trani Maria de Miguel Luken Andrea Zivi GREECE Sophia Frentzas SWITZERLAND Nikolaos Diamantis Begona Jimenez Aurelius Omlin Vasilios Karavasilis David Lorente Estellas MALAYSIA Vasiliki Michalarea Joaquin Mateo Valderrama Christos Mikropoulos Joo Ern Ang BRAZIL Victor Moreno Dionysios Papadatos-Pastos Peter Fong Andre Brunetto David Olmos Raquel Perez Alvaro Ingles Russo Desam Roda-Perez Joao Lima Laura Vidal Mariane Sousa Fontes SINGAPORE Joline Lim AUSTRALIA Matthew Ng Craig Carden Raghav Sundar Samuel Harris Daniel Tan Chooi Lee Mabel Wong Brent O'Carrigan Shahneen Sandhu CYPRUS Anastasia Constantinidou Tom Van Hagen MALTA Gert Attard

NEW ZEALAND Dean HARRIS Rajiv KUMAR