The Adult Drug Development Unit at the ICR and the RM

The Adult Drug Development Unit (DDU) at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, comprises an internationally-leading group of >100 staff focused on early anti-cancer drug development.

For all initial enquiries, site feasibility and selections, please contact one of DDU Principle Investigators. We encourage sponsors to visit the DDU at an early stages of discussion, to meet key members of our team, understand our set-up, and discuss operational considerations.

Over the years, the DDU has conducted >500 early clinical trials with our focus being on hypothesis-testing, biomarker-driven, evaluation of novel anti-cancer drugs. Several of these have now become practice-changing treatments for cancer patients including abiraterone, olaparib, afatinib, pembrolizumab, with other tested agents providing proof-of-concept including recent trials of ATR inhibition and AKT inhibition. We have developed multiple drugs generated by ICR and CRUK scientists. For example, abiraterone was first discovered and synthesized at the ICR and developed jointly with The Royal Marsden NHS Foundation Trust. Abiraterone has been hailed as one of the greatest research achievements in the history of the NHS, with the NIHR citing it as one of the top 70 discoveries that have transformed outcomes for NHS patients in a special list to mark the NHS's 70th birthday.

Collaboration is at the centre of everything we do. The ICR and DDU have a large portfolio of collaborators with over 100 industry and academic partners at any one time. We nurture our partnerships with industry. Researchers in the DDU lead the ICR and RMs partnership with the Experimental Cancer Medicine Centres (ECMC) network, made of up 18 adult centres and 11 paediatric locations across the UK. The network, established with a joint investment from Cancer Research UK (CRUK), the National Institute for Health Research (NIHR) in England and equivalents in other UK nations, brings together excellent clinical researchers across the UK. We also have multiple key industry partnerships that allow us to accelerate trial setup and establish broader relationships across multiple projects.

The Drug Development Unit (DDU) at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, comprises an internationally-leading group of >100 staff focused on early anti-cancer drug development. The DDU is at the forefront of clinical and translational cancer research and provides a key link between laboratory and clinic. It benefits from its position between the two institutions, allowing for the evaluation of a broad spectrum of novel anti-cancer agents. The DDU aims to serve as many patients as possible with diverse tumour types.

Together, as a group, we have conducted more than 500 early clinical trials, and have extensive experience in the design, regulatory submission and approval, conduct and delivery of early clinical trials for cancer patients. We have been conducting between 20 and 50 Phase 1 trials every year for over 15-years in our DDU including many investigator-initiated Phase 1 trials.

Our unit includes a separate group dedicated to sponsoring such academically sponsored trials. We also have radiology and pathology staff dedicated to our unit, as well as statistical support including access to senior statistical expertise in adaptive and Bayesian, model-based, dose-finding trials. A major focus of our group is developing methods to improve Phase 1 clinical trial designs, with a focus on the use of the Pharmacological Audit Trail, patient-reported outcomes, and making these intensive clinical trials less onerous to patient.

These trials are conducted in a purpose-built ward in The Royal Marsden; this 10-bed ward with in-patient 24-hour facilities and an outpatient facility is fully dedicated to Phase 1 clinical trials for cancer patients. It was opened in 2005, and includes single en-suite rooms for trials that require patient isolation such as oncolytic viral therapy trials for which we have established standard operating procedures. This bespoke unit fully supports the delivery of first-in-human, proof of concept, innovative clinical trials.

Our clinical trials also pursue the conduct of translational biomarker studies using, for example, next generation sequencing of tissue or liquid samples, uniplex and/or multiplex immunocytochemistry, FISH or CISH and RNAish of tumour material acquired from biopsies in our cancer biomarker laboratories. We also have extensive experience in genomic analyses of circulating tumour DNA and circulating tumour cells and utilizing apheresis as a liquid biopsy. Our overall goal is to identify as early as possible in clinical development predictive biomarkers defining which patient population the drug or drug combination can benefit.

Our clinical pharmacodynamics biomarker laboratory group, which establishes highly validated assays, operates to rigorous standard operating procedures, and works to GCP standards, is key to setting up and performing pharmacodynamics assays in normal tissue and tumour to evaluate target engagement, information that is crucial to recommending the dose and schedule of targeted agents.

Our Investigator-Initiated Trials (IIT) group (Sponsoring Group), which was established in 2012, delivers the DDU’s academically sponsored Phase I trials portfolio and has run more than 15 such trials over the last 5-years. This work is conducted in partnership with The ICR Clinical Trials and Statistics Unit (CTSU).

This group is comprised of skilled clinical research professionals to support all trials from initial discussions of trial concept, through to clinical trial protocol design and development, electronic database generation, regulatory submissions, day-to-day trial management and monitoring, data analyses and reporting, all focused on the timely delivery of high-quality ICH-GCP-compliant studies. The group brings together clinical translational scientists and biostatisticians to apply adaptive trial designs to biomarker-led early phase trials for the benefit of cancer patients.

In collaboration with commercial and academic partners our aim is to take forward promising novel anti-cancer therapeutic strategies and investigational medicinal products, including novel agents discovered at The ICR, or drug combinations which may otherwise not progress through to clinical trials. DDU’s investigator-initiated trials group fully support the operational delivery of Phase I trials from initial discussions of trial concept, through to protocol design and development, regulatory submissions, management and monitoring, to analysis and reporting.

The DDU is at the forefront of clinical and translational cancer research and provides a key link between laboratory and clinic. It benefits from its position between the two institutions, allowing for the evaluation of a broad spectrum of novel anti-cancer agents. The DDU aims to serve as many patients as possible with diverse tumour types.

Our team is fully equipped to support remote monitoring of site activities. We are able to hold remote Site feasibilities and SIVs. Our digital infrastructure provides a comprehensive, regulatory compliant and bespoke solution to enable remote verification of source data.

The Radiology department has full access to MRI, CT, PET-CT, US, and general nuclear medicine (for bone and multi-gated acquisition [MUGA] scans) facilities. Our imaging department is augmented by collaboration with research teams with a special interest in translational functional imaging at the Cancer Research UK Cancer Imaging Centre and the NIHR Cancer Imaging Clinical Research Facility (CRF). The clinical team includes dedicated experienced radiologists, nuclear medicine physicians, medical physicists and research radiographers. We have cyclotrons on site supporting PET imaging. Our team has extensive expertise in translational imaging studies utilizing PET with tracers like Zirconium and whole body MRI, as well as with magnetic resonance spectroscopy.

The analytic laboratory at the DDU is staffed by laboratory technicians and supported by a dedicated pharmacodynamics sample collection team based in the ICR. The laboratory facilitates pharmacokinetics and pharmacodynamics processing, tracking, storage and shipment to protocol requirements. The DDU has capabilities to analyse a range of biomarker samples including hair follicle, skin and archival and fresh tumour biopsies, and are able to provide sections from formalin fixed paraffin embedded (FFPE) archival tissue samples or frozen samples. On-site analysis facilities include:

Histopathology: immunohistochemistry, multi-colour immunofluorescence, fluorescence in situ hybridisation (FISH), chromogenic ISH, nucleic acid extraction from tumour tissue for DNA and mRNA analyses and tissue microarray including RNAish.
Next generation sequencing: Illumina and Ion Torrent platforms. All referred patients have their tumours evaluated with a targeted sequencing panel determining mutation analyses and gene copy number with expert bioinformatic support.
Circulating biomarker expertise: analysis of plasma DNA, circulating tumour cells, exosomes, white blood cell immunophenotyping and whole blood mRNA analyses.

We routinely seek to recruit newly referred DDU patients into molecular characterisation studies whereby patients consent to retrieval of archival and/or fresh tumour tissue for molecular testing. The clinical pharmacodynamics research group develops and runs bespoke complex pharmacodynamic assays that are crucial to the development of targeted anti-cancer drugs. They conduct these in academic and pharmaceutical company run Phase I studies.

The DDU provides a comprehensive clinical trials pharmacy service with dedicated Trials Pharmacist and Pharmacy Trials Technician staff. The Pharmacy team works closely with study teams on a day-to-day basis to ensure smooth delivery of trial services within our early phase centre.

Opened in February 2005, the DDU Ward is a purpose-designed Phase I clinical trials facility within the Royal Marsden. It provides seven day-care treatment chairs, two outpatient suites, and Oak Ward – a ten-bed inpatient ward, including two single en-suite rooms with negative pressure. The unit is staffed 24-hours a day, for at least five days a week. Based within the main body of the hospital, the unit is fully integrated with the full spectrum of clinical and support services, including the full support of the hospital’s Critical Care Team with whom we work very closely and have established standard operating procedures, for example in managing cytokine release syndrome toxicities.