Designing clinical trials personalised medicine · Designing clinical trials for personalised...
Transcript of Designing clinical trials personalised medicine · Designing clinical trials for personalised...
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om Designing clinical trials for personalised medicine
Sabine Tejpar MD PhD
University Hospital Leuven, Belgium
1-2 June 2016, Brussels
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ResearchandInnovation
Perspective
• Cancer
• Unmets needs:- Better Science
- Better return to Patients, Society
- For profit drug development
- Academia competition
• Novel models
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ResearchandInnovation
Markers of underlyingBiology
Testable hypothesisOutcomes confrontation
Clinical implications/applications
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Test a hypothesis
Did we ask the right question?Is it the right target?Is there a subgroup?
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Patient is the ultimate test tube
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Oncogenic addiction to EGFR in CRC
From Ciardiello F & Tortora G. N Engl J Med 2008;358:1160–117
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onotherapy Erbitux Unselected patients NEJM 2007
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Oncogenic addiction to EGFR in CRC
From Ciardiello F & Tortora G. N Engl J Med 2008;358:1160–117
Ras
wild type/mutant
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onotherapy Erbitux Unselected patients NEJM 2007
7 Monotherapy Kras selected patients NEJM 2008
40%
60%
HR 1
HR 0.4-0.7
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1022 tumour DNA samples (73 from fresh-frozen and 949 from formalin-fixed, paraffin-embedded tissue) from patients treated with cetuximab between 2001 and 2008 were gathered from 11 centres in seven European countries
60%, harm
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Colon Site Trends
MSI, microsatellite instability.Bettington, et al. Histopathology. 2013; Missiaglia, et al. Ann Oncol. 2014.
left right
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Tumour Location: A Predictive Marker for Cetuximab Benefit in KRAS WT?
• In CO.17 trial, left-sided primary tumour location was a strong predictor of PFS benefit in patients with KRASWT refractory mCRC treated with cetuximab
BSC, best supportive care; mCRC, metastatic colorectal cancer; PFS, progression-free survival; WT, wild type.Brule, et al. ASCO 2013.
Right-sided tumour
Cetuximab + BSCBSC only
0 5 10 15
1.0
0.8
0.6
0.4
0.2
0
Pro
po
rtio
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Time (months)
Left-sided tumour
1.0
0.8
0.6
0.4
0.2
0
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Time (months)0 5 10 15
Cetuximab + BSCBSC only
• Merck: CRYSTAL (2011)• FIRE3 (2015)• CALGB 80405 ASCO 2016• Amgen: PRIME, ….? regulatory
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Reanalysis of existing trialsCORRECT+CONCUR
Major drug trials
-test biomarker–drug interactions
VELOUR+AFLAME
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ResearchandInnovation
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ResearchandInnovation
Common structures for clinical dvlpmt?
• Big data (transversal)• Decrease trial cost, common platforms• Increase transparency• Neutrally held biobanks• Biomarker devlpmt• Adequate design (learning obj vs market acces)• Performance (control)
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Markers of underlyingBiology
Testable hypothesisOutcomes confrontation
Clinical implications/applications
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Biobanking
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ResearchandInnovation
Common structures for clinical dvlpmt?
• Big data (transversal)• Decrease trial cost, common platforms• Increase transparency• Neutrally held biobanks• Biomarker devlpmt• Adequate design (learning obj)• Performance (control)
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NCI-MATCH: A National Precision Medicine TrialConception, Development and Adjustment
Barbara A. Conley MDAssociate Director, Cancer Diagnosis Program, DCTD, NCI,
NIH
November 16, 2015
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N=1550Start 2013
PFS: HR= 0.65
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First line Second line 3rd line trial
2nd line trialFirst line Third line
1st line trial Standard treatment
Standard treatment (no open trial)
Standard treatment (no open trial)
Academia/philantropyinvestment
Industry cooperation
FundingIP-data sharing
“IVD” grade QC vs Academic Platforms
Mandatory Proven impact
nOrganisation
Regulatorystamp
European Clinical trial platform:neutrally held biobank and data repository
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ResearchandInnovation
EMA, EFPIA, Payers, EC, IMI, EORTC, academics ……..????Rest of the world?
•Pharma
Part of sampleCross comparabilty
• Neutrally held biobanks
PlatformsBiobanking, omics •Reward
Personalizedmed.