Clinical Outcomes with Multiplatform Molecular Profiling€¦ · Clinical Outcomes with...

©2016 Caris Life Sciences Confidential and Proprietary

Clinical Outcomes with Multiplatform Molecular Profiling

Andreas Voss IMI2 SGG Meeting, Brussels, September 29, 2016


Caris Life Sciences® • Headquarters: Irving, Texas

• Laboratory: Phoenix, Arizona

– 66,000 sq. ft. oncology-focused

– CLIA, CAP, NY State DOH, ISO 15189, and CE Mark

• Profiled 100,000+ patients

– 7,500+ physicians

– All 50 states

– 63 countries

• Laboratory staff

– 7 Pathologists

– 4 Molecular Geneticists

– 10 Consulting Medical Oncologists

– 4 MD and/or PhD literature evidence review team

– ~100 trained molecular & laboratory technicians


Caris Molecular Intelligence

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EVIDENCE

• Continuous study of the medical literature (>120,000 references categorized)

• Evidence Board of experts defines associations

• Only clinically validated predictive biomarkers are considered

REPORT • Substances associated with potential

benefit or lack of benefit • Reference to clinical trials • Detailed results and further reading

ANALYSIS

• Measurement of the ‘molecular fingerprint '

• High-throughput methods : < 12 days

• Highest Quality Standards • Regular updates of the test panels

INTERPRETATION • Caris Clinical Team follow up on

each case released with an executive summary of profiling findings, and with offer of telephone call


Caris Delivers Unprecedented Quality

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Pre-dissection Post-dissection

• IHC Concordance

Meetings

• IHC Threshold Monitoring

• Incidental and Unexpected

Findings Committee

• 750x Depth of Coverage

• Regular Pathologist and

Geneticist Proficiency

Training

• Non-CAP test Proficiency

Testing


Caris Clinical Evidence Procurement

• Clinical studies – 10 clinical studies with >400 patients published

– More studies ongoing

• Caris Registry Study – >3000 patients included since 2009

– Survival data from over 1200 patients reported at ECCO 2015

• Caris Center of Excellence Network (COE) – 10 large clinics in the US, 1st site in Europe opening soon

– Merge Electronic Medical Records with Molecular Database

– Time to next treatment data of >4700 patients reported at ASCO 2016

– Dynamic growth: 1400 patients profiled every month

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Patient outcomes in clinical studies of CMI

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Refractory Metastatic

Cancers

Refractory Metastatic Pancreatic

Cancers


Breast Cancers

Rare or Refractory Metastatic

Cancers

Metastatic adenoid cystic

carcinoma


Gastric Cancers


Cancers


Cancers


Cancers

PFS Ratio PFS Ratio GMI Index (PFS Ratio)

Radiol. / Biochem. Response

Clinical Benefit (CR/PR/SD>6

months) PFS Ratio

Clinical Benefit (RECIST)

PFS Ratio PFS Ratio

66

24 25

38

11

24

59

19

23

18

9 11

21

8 7

20

7

15

0

10

20

30

40

50

60

70

Von Hoff Epelbaum Jameson Dean Popovtzer Purim El Ahmadie Seeber Chahine

Nu

mb

er

Of

Pat

ien

ts

Treated with MP-guided Treatment Benefit

27% 55%

38% 44% 72% 37% 29%

34%

65%

Guided treatment administered in 74% of included patients (313/424)

Clinical Benefit in 40% of patients treated (116/289 evaluable)


Clinical outcomes: Sequencing vs. CMI

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1000 Patients Profiled

52 Patients with Clinical Benefit

1000 Patients Profiled

296 Patients with Clinical Benefit

1283

678

75

299

106

500

347

250

714

183

1144

421

66132 106

339 347

250

496

131175

21 11 36 16

12287

24

195

9

0

200

400

600

800

1000

1200

1400

Tsimberidouetal

Bedardetal Ferreiaetal Braitehetal Ganesanetal. Wheleretal Parkeretal Sohaletal LeTourneauetal

Tanabeetal

Pa entsEnrolled

Pa entsProfiled

Pa entsTreated

106

55

28

44 46

14

107

66

84

55

25

44 46

14

73

49

66

3025

38

28

11

69

19

0

20

40

60

80

100

120

VonHoffetal Epelbaumetal Jamesonetal Deanetal Purimetal Popovtzeretal ElAhmadieetal Seeberetal*

Pa entsEnrolled

Pa entsProfiled

Pa entsTreated


Registry and COE Network Studies

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1,180 evaluable patients enrolled in Caris Registry

534 Patients Matched

493 Patients Unmatched

4,729 evaluable patients from COE Network

3,011 Patients Matched

1,718 Patients Unmatched

Patients Profiled using Caris Molecular Intelligence (IHC, FISH/CISH, FA, NGS)

Performed under accreditation from CLIA, CAP and ISO5189:2012

Marshall et al. (2015) Panomics validation of time to next treatment (TNT) as a surrogate outcome measure in 4729 cancer patients. J Clin Oncol 34, 2016 (suppl; abstr 11521)

Spetzler D et al. (2015) Multi-platform molecular profiling of 1,180 patients increases median overall survival and influences treatment decision in 53% of cases. Presented at ECCO 2015


Cohort Definitions for Monotherapies and Doublet Combinations Based on Predictive Association with Biomarker Results

9 Marshall et al. (2015) Panomics validation of time to next treatment (TNT) as a surrogate outcome measure in 4729 cancer patients. J Clin Oncol 34, 2016 (suppl; abstr 11521)


Overall Survival is higher in Matched Cohort

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Matched Cohort (n=534) • Median OS 1068 days • Median 3.2 treatments after profiling Unmatched Cohort (n=493) • Median OS 646 days • Median 4.2 treatment after profiling

Spetzler D et al. (2015) Multi-platform molecular profiling of 1,180 patients increases median overall survival and influences treatment decision in 53% of cases. Presented at ECCO 2015

646 days 1068 days


Median Matched TNT is 15% (or 33 days) Longer in Caris COE Data

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Matched (n=3,011) • Median TNT = 248 days

Unmatched (n=1,718) • Median TNT = 215 days

HR = 0.85 (p=0.00018)

Marshall et al. (2015) Panomics validation of time to next treatment (TNT) as a surrogate outcome measure in 4729 cancer patients. J Clin Oncol 34, 2016 (suppl; abstr 11521)


Low High

Genomics and Proteomics are not sufficient to decipher cancer

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PCR IHC Mass Spec

NGS

Complexity & Functional Diversity


ADAPT proof of concept in plasma and tissue

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0.729

Specificity

Se

nsitiv

ity

0.0

0.2

0.4

0.6

0.8

1.0

1.0 0.8 0.6 0.4 0.2 0.0

Blo

od

-bas

ed

ass

ay

Tiss

ue

-bas

ed

ass

ay Staining with bi-directional libraries


Caris Molecular Intelligence: 1. Flexible multi-platform approach 2. Highest quality standards 3. Continuous evolution based on clinical data

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ADAPT: • Unbiased approach • Synthetically manufactured libraries • Seamless fit into todays workflows

Fulfilling the Promise of Precision Medicine

Clinical Outcomes with Multiplatform Molecular Profiling€¦ · Clinical Outcomes with...

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