2. AGENDA
The evolution towards precision, a chronology of
transition
Key topics
• Standards of care. What’s changing in therapy focus?
• Scenario-based enrollment: forecasting and validation
• Footprint of global trial activity. Who is generating the data?
KOL ranking.
• The death of the longitudinal drug development paradigm.
• Where will I be conducting my next trial?
Speaker: David Cocker, 5-6 April, 2016 | Boston Massachusetts
3. My three Vs
“Explosion of
complexity”
The complexity of cancer treatment decisions today
cannot be left in the hands of a physician only.
4.
5. Running fast and running global The oncology explosion
IMMUNOTHERAPY IS A
RAPIDLY MOVING LANDSCAPE
FIRST 3
MONTH
S
8. CONTINUAL RISE IN TRIAL ACTIVITY
407
357
250
221
282
221
293
197
87
208
119
136
118
564
559
456
424
405
333
292
268
218
210
198
181
169
0 100 200 300 400 500 600
Breast Cancer
Lung Cancer
Surgical Oncology
Head and Neck Cancer
Lung Cancer, Non-Small-Cell
Colorectal Cancer
Lymphoma
Prostate Cancer
Stomach Cancer
Non-Hodgkin Lymphoma
Pancreatic Cancer
Solid Tumors
Urinary Tract Cancer 2015 2007
Non-Hodgkin Lymphoma
Lymphoma
Lymphoma trial activity
9. CONTINUAL RISE IN TRIAL ACTIVITY
505,607
Recruiting and active trials over 10 years
435,653
Diabetes 270,607
CNS 125,000
Rare diseases
10. OUR UNDERSTANDING OF CANCER
COMPLEXITY IS INCREASING
Lung Adenocarcinoma
Operational challenge
Patient Accrual
The situation is “untenable,” says Richard
Pazdur, director of the Office of Hematology
and Oncology Products in the FDA’s Center
for Drug Evaluation and Research.
“Especially with personalized medicine
we’re going to be seeing smaller patient
numbers and it’s going to be be hard for
clinical trials to have access to patients
even if they go worldwide.”
Referring to NCI “Master Protocol”; Forbes, Nov 7, 2013
11.
12. THE EVOLUTION OF GLOBAL PLACEMENT
IMMUNO-ONCOLOGY RESEARCH
Title
The clinical trial horizon and populating study sites with an ever rarefying patient
population. US dominates phase 1 exploratory clinical sites.
61%
13. LUNG CANCER, PHASE ANALYSIS &
ENROLLMENT
Percentage %
0 20 40 60 80 100
Phase 1
Phase 2
Phase 3
Top 10
Top 50
Top 100
Enrollment
Top 50
Top 100
Top 10
US sites only, trials must have a US component
Top 100
Top 50
Top 10
Trials
Organizations
Trials
Trials
10%
22%
14. 0 10 20 30 40 50 60 70
Phase 1
Phase 2
Phase 3
LUNG CANCER, PHASE ANALYSIS &
ENROLLMENT
Percentage %
Top 10
Top 50
Top 100
Enrollment
Top 50
Top 100
Top 10
Worldwide
Top 100
Top 50
Top 10
Trials
Organizations
8%
15. Sites used EARLY phase (phase 1)
Sites used LATE phase (phase 3)
Immunotherapy trials, last 6 years
Phase 1 activity
Phase 3 activity
Phase 1 activity
Phase 3 activity
All Oncology indications last 10 years
16. ALK-1 trials generating publications in learned
societies
Footprint of global trial activity. Who is generating the data? KOL ranking.
17. INVESTIGATOR ORIGINS LUNG CANCER
Footprint of global trial activity. Who is generating the data? KOL ranking.
ASCO
2009
ASCO
2010
ASCO
2011
ASCO
2012
ASCO
2013
ECC
2013
ASCO
2014
ESMO
2014
ASCO
2015
ESMO
2015
Investigator origins lung cancer ALK-1 phase 3 ongoing trialsInvestigator origins lung cancer phase 1 ongoing trials
Set data Set data Set data Set data Set data Set data Set data Set data Set data Set data
21. The birth of the of the limited approval drug paradigm
Adapted from Dhingra K. Ann Oncol. 2015;26:2347-2350..
Key goals and criteria would include:
• Identifying a target for a drug with a well-defined MOA
• Targeting patients based on MOA
• Establishing significant efficacy in the intended use
population
o No specific minimum number of patients needed
o A higher efficacy threshold reduces the number of
patients typically required for accelerated/conditional
approval
• No unexpected non-MOA-related toxicity
• Biomarker evidence, such as PK/PD correlations
The birth of the limited approval drug paradigm
Editor's Notes
In general, we see a continual rise in trial activity for the main cancer types — with the exception of lymphoma — over the last 10 years.
