As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

1

NCCS Cancer Policy

Roundtable Meeting

Peter C. Adamson, M.D.

The Children’s Hospital of Philadelphia

Reinvigorating the Cancer Clinical Research Enterprise

Success Rates for Drug Development

Adapted from Nature Reviews: Drug Discovery, 3 (8): 711, 2004

5%

11%

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

2

NCI Cooperative Groups

A Brief History

History of NCI Cooperative Groups

1950 1960 1970 1980 1990

CCG

ECOG

CALGB

SWOG

RTOG

NWTSG

GOG

NSABP

IRSG

NCCTG

POG

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

3

1955 1965 1975 1985

CCG

SWOG Pediat. Div.

NWTSG

IRSG

POG

CALGB Pediat. Div.

History of NCI Cooperative Groups

History of NCI Cooperative Groups

Children’s Oncology Group

2000

NWTumor

SG

tudy

ational

ilms’

roup

RhabdomyosarcomaINTERGROUP

STUDY GROUP

Pediatric

Oncology

Group

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

4

• ECOG

• ACRIN

• CALGB

• NCCTG

• ACOSOG

Group Mergers

• RTOG

• NSABP

• GOG

• SWOG

New Drug Development Timelines

NCI Expanding Infrastructure

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

5

New Drug Development TimelinePre-Clinical Testing, R&D

NDA ReviewClinical R&D Post-Marketing Surveillance

Average 5 yrs (2-10 yrs)

Average 24 mos(2 mos-7yrs)

Phase 1

Phase 2

Phase 3

Short-term

Long-term

Average 18 mos (1-3 yrs)

Discovery

Initial

Synthesis

& Purification

Animal Testing

Adverse Event

Reporting

Surveys

Sampling

Testing

Inspections

IND

30 Day

Safety Review

NDA

Submitted

NDA

ApprovedFDA Time

CTEP Therapeutics DevelopmentBasic Resources Specialty Resources

/Other

Phase 1

Phase 2

Phase 3

Phase I Program(14 Phase 1 sites)

Pediatric Phase 1

Consortium

CNS Consortia

Pediatric, AdultPhase 2 Program(10 Phase 2 sites)

Cooperative

Groups*CCOPs

*Other (Centers, SPORES,

R21, R01, P01, etc.)

*Non-CTEP Funded Resources

RAID

Phase 0 - NExT

Expl IND

Courtesy of Jeffrey Abrams, MD NCI-CTEP

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

6

New Drug Development Timelines

Clinical Trials

New Drug Development TimelinePre-Clinical Testing, R&D

NDA ReviewClinical R&D Post-Marketing Surveillance

Average 5 yrs (2-10 yrs)

Average 24 mos(2 mos-7yrs)

Phase 1

Phase 2

Phase 3

Short-term

Long-term

Average 18 mos (1-3 yrs)

Discovery

Initial

Synthesis

& Purification

Animal Testing

Adverse Event

Reporting

Surveys

Sampling

Testing

Inspections

IND30 Day

Safety Review

NDA Submitted

NDA Approved

FDA Time

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

7

Clinical Development Timeline

Time (Years)

Clin

ical D

evelo

pm

ent

Phase 1

Phase 2

Phase 3

Stdy D’vpt

Study Development

∆ Rx

Concept to Trial Timeline

Process Takes up to 7 Years

National Cancer Institute

Central IRB

Re-Review

Cooperative

Group

Response

Concept

Approved

Courtesy of David Dilts

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

8

New Drug Development Timelines

Investigator Perspective

Academia

Industry

Scientific Review

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

9

Concept Incubation

Idea

•Target

•Drug

•Patient Population

Disease

Committee

Review

•Competing Ideas

•Research Landscape

Cooperative

Group

Review

•Scientific Mission

•Prioritization

•Resources

Concept

Concept to Trial Timeline

National Cancer Institute

Central IRB

Re-Review

Cooperative

Group

Response

Concept

Approved

Courtesy of David Dilts

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

10

Proposed New Organizational Structure of the Program

Fail Early

Sept-Oct 1998

Nov 1998 – July 1999

Aug 1999 - Present

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

11

“I have not failed, I have just found 10,000 ways that won’t work”

Thomas Edison

Clinical cancer research needs a system

that can strategically fail early

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

12

Cooperative Group Clinical Trials

• Efficient

• Effective

Success Rates for Drug Development

Adapted from Nature Reviews: Drug Discovery, 3 (8): 711, 2004

5%

11%

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

13

Clinical Development Timeline

Time (Years)

Clin

ical D

evelo

pm

ent

Phase 1

Phase 2

Phase 3

Stdy D’vpt

Study Development

∆ Rx

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

14

*Placebo patients who progressed could cross over to sorafenib†Including 36 patients without bidimensional tumor measurements, but with

radiological evidence of progression

Study Design: Patient Flow

Sorafenib

12-week run-in

(n=202)

Tumor shrinkage

≥25%

(n=73)

Tumor growth/

shrinkage <25%

(n=69)

Tumor growth

≥25%

(n=51†)

Off study

(n=58)

Sorafenib

12 weeks

(n=32)

Placebo*

12 weeks

(n=33)

Continue open-

label sorafenib

(n=79)

% Progression

free 24 weeks

Disease status at

12 weeks unknown

(n=9)

Courtesy of Mark Ratain, MD

Progression Free Survival: Randomized Patients

Pro

po

rtio

n o

f p

ati

en

ts p

rog

ressio

n f

ree

0

0.25

0.50

0.75

1.00

Time from randomization (weeks)

0 6 12 18 24 36 48 60 66

Sorafenib

Placebo

Censoredobservation

Median PFS

Sorafenib = 24 weeks

Placebo = 12 weeks

Hazard ratio (S/P) = 0.44

p-value <0.000001

54

Courtesy of Mark Ratain, MD

As Presented at the NCCS Cancer Policy Roundtable

October 18-19, 2011

15

Smart Drugs

Smart Trials