HJMUKMF Spring Day – 13 March 2013 Early Phase Clinical Trial Network UKMF Spring Day - 13 March 2013

HJMUKMF Spring Day – 13 March 2013 CTN Objectives Strategic The most pertinent clinical studies are identified based on Key Objectives and developed and prioritised by a Steering Group of myeloma specialists. Collaborative Stakeholders throughout the NHS, HTA, Patients and the Pharmaceutical Industry work together to implement the most effective clinical trial design and ensure effective adoption of data. Efficient Working as a network, coordinated via a central office with standard processes and procedures and working with NHS and industry stakeholders, the CTN aims to break down the barriers that delay research enabling studies to be delivered quickly and effectively.

HJMUKMF Spring Day – 13 March 2013 Bringing Stakeholders Together Clinical Experts Leeds Clinical Trials Coordinating Office

HJMUKMF Spring Day – 13 March 2013 CTN Network Leeds Clinical Trials Coordinating Office St James’s, Leeds City, Nottingham QE, Birmingham The Christie, Manchester RMH, London UCLH, London King’s, London Bart’s, London R Hallamshire Sheffield General H, Southampton Uni H Wales, Cardiff Uni Hospital, Oxford Central Trial Office 8 Core Active Trial Centres 4 Additional Centres Expansion inc. Scotland & N Ireland

HJMUKMF Spring Day – 13 March 2013 CTN is part of a wider objective Other areas include: Improving the setting for adoption of non-commercial data Making best use of available resources, especially patients Promote novel clinical trial designs Supporting novel approaches to licensing e.g. adaptive licensing Developing novel drug life-cycle strategies Addressing health economic barriers Collaboration with pharmaceutical companies Development of “Pathways Model” to identify future optimum therapy CTN trials are one part of a wider Myeloma UK objective to impact how clinical trial data is generated and adopted, to more effectively bring optimum treatments to patients.

HJMUKMF Spring Day – 13 March 2013 Strategic Approach to Selecting Trials Personalised Medicine Individualised treatment based on diagnostic biomarkers (i.e. genetic subgroups) Individualised treatment based on clinical presentation (clinical subgroups e.g. elderly/frail, high risk) Access to Treatments Promoting novel treatments Identifying evidence gaps for drugs currently in development that may prevent or delay them being approved by NICE and/or taken into UK practice. Planning studies around expected life-cycle of a drug in real world setting CTN trials are identified and prioritised based on two objectives:

HJMUKMF Spring Day – 13 March 2013 Current Portfolio of MUK Trials MUK No. Test DrugTitleStatus MUK one Bendamustine (Napp) An open label, multi-centre, randomised, parallel group phase II selection trial to identify the optimal starting dose of bendamustine (60 vs 100 mg/m 2 ) when given in combination with thalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. COMPLETED patient recruitment, in analysis MUK three CHR3996 & Tosedostat (Chroma) A Phase I/IIa, Dose-Escalation, Study of CHR-3996 in Combination with Tosedostat in Subjects with Relapsed, Refractory Multiple Myeloma. OPEN Recruiting patients to Phase I MUK four Vorinostat (MSD) An open label, single arm, phase II trial to assess the efficacy, safety and tolerability of vorinostat in combination with bortezomib and dexamethasone (VVD) in patients with relapsed or relapsed refractory multiple myeloma. Expected to open 2Q 2013 MUK five Carfilzomib (Onyx) A phase II randomised trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs cyclophosphamide, Velcade and dexamethasone (CVD) for first relapse in myeloma patients. OPEN Recruiting patients MUK six Panobinostat (Novartis) A Phase I/IIa trial of Velcade, thalidomide and dexamethasone (VTD) with panobinostat in relapsed and relapsed/refractory multiple myeloma patients who have received 1-4 prior lines of therapy. OPEN Recruiting patients to Phase I Pomalidomide (Celgene) Pomalidomide Specific Targeting in Relapsed and Refractory Myeloma (POST Study). A single arm Phase II study in which all patients will receive treatment with Pomalidomide and Dexamethasone. Expected to open 3Q2013

HJMUKMF Spring Day – 13 March 2013 CI and Co-Investigators StudyDrugCICo-investigator MUK oneBendamustineSScheyJ Cavet MUK threeCHR3996 & TosedostatFDaviesGMorgan & KYong MUK fourVorinostatFDaviesCWilliams & JCavet MUK fiveCarfilzomibKYongGMorgan & CWilliams MUK sixPanobinostatJCavenaghGMorgan & KYong MUKPomalidomideGMorganFDavies & GCook

HJMUKMF Spring Day – 13 March 2013 Linking the CTN with Discovery Research Diagnostics Biobanking Clinical Trial Network     Myeloma Research Centres Personalised Medicine Programme

HJMUKMF Spring Day – 13 March 2013 Why the MUK CTN important Patients are waiting… Myeloma patients need more effective treatments with less side-effects. In order to deliver this in the soonest possible time frame, we have set up the CTN to be more efficient and more effective. We must challenge the hurdles and the inefficiencies and strive for improvements in the system.

HJMUKMF Spring Day – 13 March 2013 “Our Clinical Trial Network is a groundbreaking approach to clinical research in the UK. It is strategic, efficient and collaborative. Our model of engaging with stakeholders and breaking down barriers is not only changing the course of myeloma research, but could transform the way in which new treatments for other rare cancers are tested and accessed.” Eric Low OBE, CEO Myeloma UK