Experimental Cancer Medicine Centres (ECMC) Network A year of progress 2014/15 £70m The capacity committed to developing of the ECMC infrastructure for early phase trials Network to date 9 Paediatric Launched in 2007, the Experimental Cancer Medicine Centres Centres The ECMC Network supports a selection of the best (ECMC) Network is jointly funded by Cancer Research UK science and experimental therapeutics at the forefront and the health departments for England, Scotland, Wales of cancer research in the UK Edinburgh and Northern Ireland Glasgow & Dundee ECMC funding supports over 200 staff members involved in The ECMC initiative supports the infrastructure needed to translational research and early phase trials, including research number of trials by cancer type both deliver world-leading early phase clinical trials and to enable nurses, operational staff, pharmacists, physicists, radiographers, supported by the ecmcs (2012/15) haematology 181 a network of experts to translate scientific discoveries into new Newcastle pathologists, trial coordinators and quality assurance staff. cancer treatments for patients. any advanced cancers 140 With a total of 124 new trials reported, the year 2014/15 saw lung 76

This booklet highlights just some of the ground-breaking Belfast progress in a wide spectrum of treatment and modalities and breast 71

achievements made in the ECMC Network during the disease sites. colorectal 46 Leeds financial year 2014/15. melanoma 37 Progress prostate 32 Manchester in a wide multiple tumour types 30 Liverpool pancreas 28 “We’re delighted Sheffield spectrum of that our ECMC Network treatment and brain & nervous system 28 Introduction ovarian/fallopian tube 25 has been able to support modalities and new trial by treatment added to the network (2014/15) renal 23 this important initiative to Leicester disease sites Birmingham small molecules 105 head & Neck 17 streamline the regulation of clinical immunotherapy 13 liver 17 research, so patients can continue Cambridge biomarker 5 soft tissue 15 to reap the benefits from the observational 3 oesophageal 14 Oxford world-class research taking place 18 imaging 3 bladder 12 Cardiff Adult London: Barts & Brighton gene therapy 1 mesothelioma 8 throughout the UK” Bristol Centres ICR radiotherapy 1 uterine/endometrial 6 Prof Peter Johnson Imperial device 1 stomach 5 Cancer Research UK Southampton KCL chemotherapy 1 bone 5

UCL other 12 other 57 A Network committed to This year saw some great examples of the innovation groundbreaking work that ECMC Network staff Scientific can deliver, with a broad range of innovative excellence trials taking place within the Network that benefits Case Study: Harmonisation of cell-free DNA (cfDNA) practices patients Cell-free DNA (cfDNA, sometimes referred to as circulating tumour DNA TRACERx or ctDNA) is a promising blood-based biomarker. Research in cfDNA is HIPROC A biomarker study growing with many new trials collecting plasma for analysis, but to date, there A Phase I/Ib trial to to track genomic lung is no consensus on techniques, analysis, priority research questions and clinical test a hedgehog inhibitor cancer evolution Immunobody strategy to validate cfDNA as a diagnostic or prognostic marker for cancer. (LY2940680) in combination (18 ECMCs) A phase I study to test with paclitaxel in patients a DNA vaccine encoding Understanding the critical importance of harmonising research techniques with ovarian cancer a human modified IgG1 to be able to compare results and advance in this promising field, ECMC (Glasgow, Imperial, Barts antibody in melanoma researchers and clinicians met to agree on a common research strategy. & Brighton ECMCs) (Leeds, Manchester, Newcastle, Southampton ECMCs) Consensus

34 meeting held in Case Study: NIMRAD attendees November 2014 The NIMRAD trial aims to understand the effect of combining 14 co-hosted by 4 radiotherapy with the drug nimorazole for people with locally ECMCs ECMC Secretariat industry advanced head and neck cancers. Radiotherapy is commonly used to and NCRI* partners treat patients suffering head and neck cancer and this study assesses the impact of adding a drug (nimorazole) that targets cells with low levels of oxygen (more difficult to kill with radiotherapy). The study Outcomes of the meeting: is a national multi-site trial funded by Cancer Research UK (CRUK) • An agreed set of recommendations on analysis, techniques and and led by Manchester ECMC with the participation of 6 ECMCs: ‘gold’ standard practice needed to advance research in cfDNA Birmingham, Cambridge, Glasgow, ICR, Leeds, and Sheffield. • The development of a systematic review and sample sharing study In addition, with the collaboration of Belfast, Birmingham, Cambridge, funded by the ECMC initiative Cardiff, Glasgow, ICR, Leeds, Newcastle and Sheffield ECMCs, • A shared plan to develop standard operating procedures (SOP) Manchester ECMC also led NIMRAD-TRANS to prospectively to share across the ECMC Network and beyond to the UK and qualify hypoxia gene signatures to predict nimorazole plus

* National Cancer Research Institute international research community radiotherapy benefit in head and neck cancer patients. KHP PIONEER Glasgow is Glasgow Edinburgh a Phase I study of Leicester ECMC is recruiting & Dundee ECMC olaparib in combination with Belfast for the MADCAP study, developed Olaparib chemo-radiation in locally advanced which is a Phase I/randomised from Phase I to Phase III. The pancreatic cancer. Under the NIHR Phase II trial of abiraterone acetate European Medicines Agency Alliance initiative, the Glasgow ECMC has with or without RO5503781 in patients approved Olaparib for use in developed this multi-site study to assess with metastatic castration resistant Europe in December 2014. It is whether adding olaparib (AZD2281) to prostate cancer. MADCAP results licenced for women with advanced a capectiabine-based chemo-radiation will establish whether the addition of ovarian cancer, fallopian tube regimen improves the effects of RO5503781 to the abiraterone regime and peritoneal cancer who treatment in this subgroup of patients improves radiological progression- carry a faulty BRCA1 or Oxford with locally advanced pancreatic free survival (PFS) in patients BRCA2 gene. Belfast ductal adenocarcinoma. with metastatic prostate Newcastle 11 European cancer. partners ECMC ran a This study to successful investigator-led analyses the effects imaging trial called FLAIRE Innovation of Vitamin D treatment MERCURIC using 18F-FLT PET CT to assess Collaboration on growth control biomarkers Glasgow Edinburgh study (funded by response to radiotherapy. The trial in human primary colorectal & Dundee the European Union) has completed recruitment and the Belfast tumours (CRT). Once the is a phase Ib/II trial to results show that FLT PET CT Leicester optimal dose of Vitamin D is Sheffield assess a novel therapeutic Birmingham imaging during radiotherapy is defined in Belfast ECMC, the ECMC led the strategy and search for a potential biomarker for trial will expand to include completion of successful novel biomarkers in early response to Leicester the Birmingham and phase I escalation trial The colorectal cancer. Newcastle treatment. ECMC Leicester ECMCs. CHART-ED in non-small cell lung team, in cancer, which informed the design collaboration with Imperial of new studies such as ADSCaN ECMC, have shown that cell Using EBV+ free DNA (cfDNA) monitoring Selumetinib in - a randomised phase II study The can detect emergence of Leeds Iodine Refractory of accelerated, dose escalated, cancer program led Birmingham ECMC resistance to endocrine Oxford Differentiated Thyroid sequential chemoradiotherapy by in non-small cell lung developed a therapeutic therapy in patients with Glasgow Cancer. This is sponsored cancer (NSCLC). vaccine comprising a recombinant ER+ breast cancer. by Sheffield and vaccinia virus, MVA-EL, to boost The ECMC- co-ordinated by Belfast Leeds immunity to EBV antigens. A funded biomarker A Phase I trial to Leeds CTRU. Sheffield Cardiff Sheffield phase I trial was conducted and programme has collected test the safety and Glasgow successfully showed that MVA- more than a 1,000 normal and The Opportune benefit of pre-operative Southampton EL is safe and immunogenic tumour specimens from melanoma study, which is a stereotactic body radiation Edinburgh & across diverse patients and normal tissue from healthy randomised Phase II (SBR) therapy for previously Dundee Oxford ethnicities. volunteers. The resources allowed window study to test untreated borderline Newcastle researchers at KHP to describe humoral GDC0941 plus Anastrozole The creation of Birmingham Leicester operable pancreatic Southampton responses in melanoma patients with versus Anastrozole alone in cancer. a UK network for Birmingham pre-clinical drug therapy BRAF mutations, resulting in the patients with ER+ primary UCL identification of novel immune breast cancer. assessment using “organoids”. biomarkers Organoids, derived from the In collaboration with for predicting Cambridge GI Solutions and Medtronic, malignant disease Developing a tumours of cancer patients ICR closely replicate key properties this trial has developed a non- outcomes. A Phase I trial for technique of preparing endoscopic diagnostic test for ECMC was the KHP transplantation of the original tumours and patients with locally patients for Barrett’s oesophagus using a device lead site on the ECMC Barts & using a radio-labelled are amenable to large- Brighton advanced or metastatic called the Cytosponge combined with Combinations Alliance trial monoclonal antibody scale drug screens. tumours. Patients will that London the Barrett’s specific biomarker TFF3. ComPAKT with AZD2014, a vandetanib receive the drug targets the bone marrow allowing The positive results from the intial novel oral m-TORC 1/2 inhibitor. in combination with targeted very precise delivery of high trials have encouraged the Cambridge After successful treating 56 131I-mIBG radiotherapy ( ) to radiation doses to the site of team to perform a randomised patients, the trial has progressed London determine the recommended disease, in this case the to Phase II, as well as a new Manchester controlled trial of Ctyosponge- dose of vandetanib for clonal plasma cells. TFF3 in primary care. Phase I/II trial called TAX- KHP Phase II. TORC combining AZD2014 Both adult and paediatric ECMCs continue to use their Networking infrastructure and work carried out through the ECMC initiative to leverage additional funds from pharmaceutical companies, biotech companies, government and other partnerships. As a result, this year has seen 48 companies involved in setting up new partnerships with the ECMCs which has resulted in over £73,400,000 The ECMCs have established themselves and become a key of leveraged funds. component of the cancer research infrastructure in their locations throughout the UK. Boehringer-Ingelheim Vertex The number of multi-site trials has increased by a third since the launch Ocello Almac-Discovery-Ltd of the ECMC Initiative in 2007.

Genenbech Basllea Transgene Biotecnol-Ltd Pfizer ParExel Autolus-Syncona The collaborative nature of the Network would not be possible without Aprea-AB Elsal-Ltd AstraZeneca Quintiles Roche Ono-Pharma Shionogi the sense of community that stems from the different ECMC professionals. Merck

Nucana Celgene ACERTA Bayer Affibody MedImmune

The ECMC community share best practices, through the 6 ECMC Network Qiagen Astellas Verastem Bioinvent Dohme Leucid-Bio

GE-Healthcare Algeta-Bayer

Affymetrix-TSB GSK

Incanthera Sharpe CRT groups, training opportunities across ECMCs and collaboration in major Cell-Therapy-Catapult Novartis Innovate-UK

initiatives such as the Lung Matrix Trial. Centre Sarah-Canno-Research PsiOxus-Therapeutics-Ltd London-Pharma Pierre-Fabere PPD Immunocore Myriad-Genetics Nordic-Nanovector Sixth-Element-Capital The 6 ECMC Network Groups: Case Study: The Trial Harmonisation Programme Biomarin-Pharmaceuticals The Trial Harmonisation Programme in an initiative to streamline Research trial delivery for UK-wide early phase cancer studies by establishing Nurses Cellular & a single operational framework across all ECMCs. This ambitious Molecular Junior UK Programme aims to enable the consistent and unified management Developing Pathology (CMP) Investigator Radiopharmacy of trials processes across the Network. Network Group Group Taskforce Recognising the importance of standardising practices and reducing Partnerships (JING) UK (CERT) set up times to ensure that the UK remains competitive in the Therapeutic global market, we have worked in partnership with the Health Quality Cancer Research Authority (HRA) to streamline pharmacy and medical Assurance & Prevention exposure reviews across the Network. Translational Network Science (QATS) (UKTCPN) During 2014/15, the ECMC Network volunteered to pilot this initiative which will later be rolled out to the rest of the country. The resulting success was well received by researchers, clinicians, R&D staff and industry stakeholders. A diverse Over 2500 patients trial portfolio were recruited This year we have seen the development and progression onto 389 trials of some exciting trials throughout the ECMC Network. supported by the Our trial portfolio covers a broad range of cancer types as well ECMC Network as treatment modalities. See below a snapshot with some examples in 2014/15 of the diversity of trials taking place in the Network in 2014/15.

/ tissue pre - clinical P H ASE 0 P H ASE I P H ASE II P H ASE III P H ASE I V biomarker T reatment y modalit cancer Ty pe / tissue pre - clinical P H ASE 0 P H ASE I P H ASE II P H ASE III P H ASE I V biomarker T reatment y modalit cancer Ty pe LSD1 inhibitor AZD2014 all Pan –HER inhibitor Pazopanib +/- Fosbretabulin Anti microbial agent PI3k-beta inhibitor (GSK2636771) All Tubulin/microtubule inhibitor prostate with enzalutamide Rucaparib AZD5363 ATKI Fulvestrant +/- vandetanib Acelarin first in class nucelotide PIK3CAi GDC0032 with Tamoxifen P13K beta & delta inhibitor breast AZD4547 with anastrozole or letrozole prostate Olaparib LEE001 with fluvestrant Breast Fulvastrant & BYL719 or BMK120 HSP90 inhibitor VTD- panobinostat haematological FLT3/JAK2 inhibitor treatments tefinosta haematological Daratumumab with Lenalidomide

small molecule lymphoma Pan P13K MTOR inhibitor & Dexamethasone AZD9291 CHR-3996 with Tosedostat

lung Afatnib combination drug SMP2/Matrix LDK378 ALK inhibitor AZD2014, pacitaxel lung melanoma Vismodegib AZD6244 (MEK-Inhibitor) oesophagus Somatostatin analogue lanreotide, ADIPemCis inhibit THS secretion melanoma DTIC and plitidespin ovarian Olaparib Metronomic-cyclophosphamide breast 18F ICM11 PET ovarian +/- nintedanib (BIBf 1120) lymphoma 18F ICMT11 PET colorectal Stratification of KRAS, BRAF 18F ICMT11 PET & topo-1 lung 18F-D4-Flurocholine PET/CT immuno LUNG MPDL3280A imaging bladder 18F-D4-Fluorocholine PET/CT therapy bladder MPDL3280A all HuMax TF-ADC immunoconjugate Continuous hyperfractionated radiotherapy LUNG Monoclonal Pembrolizumab accelerated radiotherapy Antibody melanoma Pembrolizumab all Cannabinoid, dexanabinol prostate Prognostic assay LUNG Lung-sparing surgery surgery New diagnostic oesophagus Cystosponge- diagnostic device colorectal Eicosapentaenoic

Volasertib, inhibitor of PLK1 protease h er ot acid &/or aspirin children’s Blinatumomab IHC, Omic, CTCs paediatric ovarian cancers Anti-GD2 given as long-term DNA methylation infusion with IL2 Generated a new study Experimental Cancer Medicine Centres (ECMC) Network Cancer Research UK Angel Building 407 St John Street London, EC1V 4AD 020 3469 5381 [email protected] www.ecmcnetwork.org.uk @ECMC_UK The Experimental Cancer Medicine Centres Initiative is jointly funded by Cancer Research UK, the National Institute for Health Research in England ECMC-Experimental-Cancer-Medicine-Centres and the Health Departments for Scotland, Wales and Northern Ireland.