Key factors in trial design

Ruth Plummer (with thanks to Bob Brown and Will Steward)

JING meetingJanuary 2016

1

Overview

• NOT going to talk about phase I, II and II trials and their design

• Focus on translational trials which would fit in ECMC portfolio– Combinations alliance– NAC trial grants– (CDD projects)

• Some comments on application strategy

2

Health warning

• These are my views and advice – not NAC or CDD policy

• Based on NAC membership then chairmanship

• NAC chair does not currently score proposals, I can try and guide discussion and propose solutions

• CDD/JSC has prepared a briefing document outlining key factors which will be discussed fully at February’s NAC

3

Combinations Alliance Responsibilities

TC Workshop Review Delivery

JSC JSC NAC JSC

0 1 2 3 4 5 6 7 8 9 10 11

*Lung

*Oesophageal/H&N

Breast

Ovarian

*Pancreatic

Adult leukaemia/myeloma

Colorectal

Lymphoma/Hodgkins

Paediatric

Prostate

Any solid tumour

*Brain

Bladder

Melanoma

Sarcoma

Renal

Liver

CNS DD Projects

NAC Trial Grants/Endorsements

* Priority areas in CR-UK's strategy

NAC-approved trials - tumour types

Oct 20155

CDD Portfolio – breadth of possible projects

Oct 20156

Drug-Drug

9

Drug-Antibod

y5

Drug-RT4

Drug-Drug-RT

2

Ab-Ab-RT1

Ab-RT1

Types of Combination Therapy in CDD Preclinical Portfolio

PARP

Wee1MEKVEGFR

EGFR

mTOR

MCT1HSP90

CDK4/6ALK

CCR4

AGCCD40

CD20TLR

ATR

Proteosome

TKsHHPI3KBTK

PD1CTLA4

HER2

Targets in CDD Preclinical Portfolio

PARP

MEK

FGFR

mTOREGFR ErbB

HDAC

PI3K

HSP90

AKT

ATR

TKsHH

Aromatase

DNMTBTKFAK

WEE1

Targets in CDD Trial Grant Portfolio

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(and stop you looking foolish)

Generally people like to help

EOI Combinations Alliance Guidance Document

Guidelines for supportive preclinical and

translational data under development

• Once discussed at NAC in February 2016 will go on website as advisory document

• NOT a scoring system

• Suggested criteria to be considered for an application

• Indication as to whether add strength to application

• Will show high, medium or low value

• Absent data allowed (but give a reason!)

20

What the committee dislikes

• Careless submissions start you off on the wrong foot– Typos– Obvious cut and paste errors

• “No biomarker no trial” – but not too many• Lack of a validation plan (lack of realism)• Don’t miss out the key safety data (show it

matters to you)• Huge appendices and then non-specifically

referring to them• Build a credible team and get a mentor

21

Thank you and any questions

22