The Patient Journey Planner: an integrated approach to trials of targeted therapies with application to cancer and haematological malignancies Robert Hills1, Nigel Russell2, Kerry Hood1, Girish Patel3, Richard Adams1 1 Centre for Trials Research, Cardiff University, Cardiff UK; 2 Nottingham University Hospitals NHS Trust, Nottingham UK; 3 Cardiff and Vale UHB, Cardiff UK

Background Large simple trials have advantages Wide eligibility Real-life Easy to participate in Allow detection of moderate treatment effects But increasingly, conditions are becoming more delineated Smaller groups of patients Disease doesn’t stay the same (clonal evolution) Requires identification of what targeted treatment may be helpful What is best for a patient may change as time goes on

Challenges of an all-comers trial

AML: a suitable case for treatment?

NCRI AML17 Trial Pacritinib on relapse viii

NCRI AML17 Trial viii Pacritinib on relapse Monitor Marker identified ix No monitor

Breaking this down… What is the best induction treatment? Based upon emergent risk factors … Is a suitably targeted therapy beneficial? Is treatment intensification worthwhile in high risk patients? Does monitoring disease levels allow for early intervention for relapse – and is it beneficial? In patients who relapse What is the best therapy? Does the targeted therapy Pacritinib show promise in patients with a FLT3 mutation?

In other words… What is best at a given stage in the patient journey? Trial presents the information relevant to a patient at that stage in their journey – just as in a clinical consultation 70% of all younger patients enter this protocol

Dealing with targeted therapies Prompt identification of targets (see poster by Betteridge) Umbrella trial But groups may be very small Master protocol “Treatment” Trial 1 “Treatment” Trial 2 “Treatment” Trial 3 “Treatment” Trial 4 “Treatment” Trial 5

Marquee trials Interim review for futility of new therapies – rotation of therapies in the trial (see Thomas – next talk)

Patient Journey Planner Available options depend on patient stage; previous treatments; biomarkers Option Option Option Option Induction Option Option Option Option Consolidation Option Option Option Option Transplant Option Option Option Option Maintenance Option Option Option Option Relapse/ Refractory

Patient Journey Planner  Option Option Option Option Induction Option Option Option Option Consolidation Option Option Option Option Transplant Option Option Option Option Maintenance Option Option Option Option Relapse/ Refractory

Patient Journey Planner Option  Option Option Option Induction Option Option Option Option Consolidation Option Option Option Option Transplant Option Option Option Option Maintenance Option Option Option Option Relapse/ Refractory

Patient Journey Planner Option  Option Option Option Induction Option Option Option Option Consolidation Option Option Option Option Transplant Option Option Option Option Maintenance Option Option Option Option Relapse/ Refractory

Patient Journey Planner Option  Option Option Option Induction Option Option Option  Option Consolidation Option Option Option Option Transplant Option Option Option Option Maintenance Option Option Option Option Relapse/ Refractory

Patient Journey Planner Option  Option Option Option Induction Option Option Option  Option Consolidation Option Option Option Option Transplant Option Option Option Option Maintenance Option Option  Option Option Relapse/ Refractory

Skin Cancer Patient Register Beyond AML Skin Cancer Patient Register Prevention Tenovus sun avoidance British Skin Foundation Sun awareness   Screening CDNK2a MCR1+ Ocular melanomas Others Adjuvant treatment (high risk) Alpha interferon Immune checkpoint inhibitors (node +ve) Immune checkpoint inhibitors (thick melanomas) Oncogene targeted therapy BRAF + NRAS c-KIT NF-1 GNAQ Immune checkpoint inhibitor ipilimumab pembrolizumab novilumab others combos Tumour vaccine studies CARS Melanoma Antigen Immunotherapy Supportive Care/QoL

Conclusions NCRI AML Working Group trials already use the Patient Journey Planner approach Requires joined up information Real time marker identification Centralised IT to determine eligibility Allows cross trial group collaboration Different treatments at different stages of development at different points on the journey Adaptable to other conditions @CTRCardiffUni