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SPECIMEN INFORMATION
Ordering Physician Name
The Cancer Center
1234 Main Street
Dallas, TX 12345
(123) 456-7890
SE
.
Primary Tumor Site: Lung, NOS
Specimen Site: Lung & Bronchus
Specimen Collected: XX/XX/2012
Specimen Received: XX/XX/2013
Initiation of Testing: 1/15/2013
Completion of Testing:
Specimen Id: XYZ-123
IC
Case Number: TN13-111111
Date Of Birth: XX/XX/2005
Sex: Female
U
Patient Name
ORDERED BY
AL
PATIENT
cisplatin, carboplatin
erlotinib
irinotecan
gemcitabine
doxorubicin, liposomaldoxorubicin, epirubicin
NRAS
BRAF
KRAS
imatinib
GNA11
IV
E
AT
VHL
ST
R
trastuzumab
LU
lapatinib
vemurafenib
EGFR
Her2/Neu
sunitinib
temozolomide, dacarbazine
PIK3CA
nab-paclitaxel
PU
gefitinib
PO
SE
cetuximab
TM
R
OFF NCCN COMPENDIUM
S
O
docetaxel, paclitaxel
fluorouracil, capecitabine,
pemetrexed
N
LY
.
crizotinib
TM
ON NCCN COMPENDIUM
Potential Targets
Associated
with CLINICAL TRIALS
T
Agents Associated With
Potential LACK OF BENEFIT
MI-2013-01-26.0
N
O
Agents Associated with
Potential BENEFIT
FO
R
C
LI
N
Molecular Intelligence NSCLC Comprehensive PLUS NGS
Panel Summary
EP
O
R
T.
IL
everolimus, temsirolimus
SA
M
PL
E
R
The selection of any, all or none of the matched agents resides solely with the discretion of the treating physician. Decisions on patient care and treatment must
be based on the independent medical judgment of the treating physician, taking into consideration all applicable information concerning the patient’s condition,
such as patient and family history, physical examinations, information from other diagnostic tests, and patient preferences, in accordance with the applicable
standard of care. Decisions regarding care and treatment should not be based on a single test such as this test or the information contained in this report.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
Clinical History
SE
.
Adenocarcinoma of the lung.
IC
AL
U
Submitted Pathologic Diagnosis
Adenocarcinoma of the lung.
LI
N
Specimens Received (Gross Description)
The specimens consist of:
FO
R
C
1 (A) Paraffin Block - Client ID (XYZ-123).
Interpretation (Caris Life Sciences Microscopic Diagnosis):
N
O
T
Adenocarcinoma of the lung.
LY
.
Electronic Signature
PO
SE
S
O
N
By my electronic signature, I as the attending pathologist affirm that I have personally reviewed and examined microscopically the prepared slide(s)
and that the above diagnosis has been made or confirmed by me.
Disclaimer
E
PU
R
All of the individual assays that are available through Caris Life Sciences® Molecular Intelligence™ Services (Caris Molecular Intelligence) were developed and validated by Caris
MPI, Inc. d/b/a Caris Life Sciences and their test performance characteristics were determined and validated by Caris Life Sciences pursuant to the Clinical Laboratory Improvements
Amendments and accompanying regulations ("CLIA"). Some of the assays that are part of Caris Molecular Intelligence have been cleared or approved by the U.S. Food and Drug
Administration (FDA). The clinical reference laboratory of Caris MPI, Inc. is certified under CLIA to perform high complexity testing, including all of the assays that are part of the
Caris Molecular Intelligence.
ST
R
AT
IV
The CLIA certification number of each Caris MPI, Inc. laboratory performing testing in connection with Caris Molecular Intelligence can be found at the bottom of each page. This
Report includes information about therapeutic agents that appear to be associated with clinical benefit based on NCCN Compendium guidelines, relevance of tumor lineage, level of
published evidence and strength of biomarker expression, as available, reviewed and assessed by Caris Life Sciences. The agents are not ranked in order of potential or predicted
efficacy. The finding of a biomarker expression does not necessarily indicate pharmacologic effectiveness or lack thereof. The agents identified may or may not be suitable for use
with a particular patient and the report does not guarantee or suggest that any particular agent will be effective with the treatment of any particular condition. Caris Life Sciences
expressly disclaims and makes no representation or warranty whatsoever relating, directly or indirectly, to this review of evidence or identified scientific literature, the conclusions
drawn from it or any of the information set forth in this Report that is derived from such review, including information and conclusions relating to therapeutic agents that are included
or omitted from this Report.
IL
LU
The decision to select any, all or none of the matched agents resides solely with the discretion of the treating physician. Decisions on patient care and treatment must be based on
the independent medical judgment of the treating physician, taking into consideration all applicable information concerning the patient’s condition, such as patient and family history,
physical examinations, information from other diagnostic tests, and patient preferences, in accordance with the applicable standard of care. Decisions regarding care and treatment
should not be based on a single test such as this test or the information contained in this report.
EP
O
R
T.
The information presented in the Clinical Trials Connector™ section of the Report is compiled from sources believed to be reliable and current. We have used our best efforts to make
this information as accurate as possible. However, the accuracy and completeness of this information cannot be guaranteed. The contents are to be used for clinical trial guidance
and may not include all relevant trials. Current enrollment status for these trials is unknown. The clinical trials information present in the biomarker description was compiled from
www.clinicaltrials.gov. The contents are to be used only as a guide, and health care providers should employ clinical judgment in interpreting this information for individual patients.
Specific entrance criteria for each clinical trial should be reviewed as additional inclusion criteria may apply. Caris Life Sciences makes no promises or guarantees that a healthcare
provider, insurer or other third party payor, whether private or governmental, will provide reimbursement (instead of coverage) for any of the tests performed.
SA
M
PL
E
R
The next generation sequencing assay performed by Caris Life Sciences examines tumor tissue only and does not examine normal tissues such as tumor adjacent tissue or whole/
peripheral blood. As such, the origin of any mutation detected by our assay may either be a somatic (not inherited) or a germline mutation (inherited) and will not be distinguishable
by this assay. It is recommended that results be considered within the clinical context and history of the patient. If a germline inheritance pattern is suspected then counseling by
a board certified genetic counselor is recommended.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
SE
.
Agents Associated with Potential BENEFIT
Result
cMET
FISH
Not Amplified
1.00
✔
cMET
IHC
Negative
1+ 45%
✔
EGFR
Next
Gen SEQ
Pathogenic
E746_A750del
✔
KRAS
Next
Gen SEQ
Pathogenic
G13D
PIK3CA
Next
Gen SEQ
Pathogenic
H1047R
PTEN
IHC
Positive
2+ 60%
PGP
IHC
Positive
2+ 30%
✔
29, 30
TLE3
IHC
Negative
1+ 5%
✔
31, 32
TUBB3
IHC
Negative
TOPO1
IHC
Positive
Her2/Neu
CISH
PGP
IHC
docetaxel, paclitaxel
C
LI
N
IC
4, 5, 6, 7
✔
3, 4
9, 10
8
✔
S
O
N
LY
.
N
O
T
FO
R
1, 2
33, 34, 35
Amplified
5.00
✔
38, 39
Positive
2+ 30%
✔
43, 44
FISH
Not Amplified
1.00
✔
39, 40,
41, 42
IHC
Negative
1+ 30%
✔
45, 46
Her2/Neu
CISH
Amplified
5.00
✔
53, 54,
55, 56
Her2/Neu
IHC
Negative
1+ 25%
Her2/Neu
CISH
Amplified
5.00
Her2/Neu
IHC
Negative
1+ 25%
BRAF
Next
Gen SEQ
Pathogenic
V600E
R
AT
IV
E
PU
R
✔
LU
IL
T.
vemurafenib
9, 11
2+ 80%
R
R
SA
M
PL
E
lapatinib
Lack of
Potential
Benefit
26, 27, 28
MGMT
EP
O
trastuzumab
Decreased
Potential
Benefit
✔
TOP2A
temozolomide,
dacarbazine
Potential
Benefit
1+ 20%
ST
doxorubicin,
liposomaldoxorubicin,
epirubicin
✝
Value
AL
Method
erlotinib, gefitinib
irinotecan
Data
Reference
Level*
Test
PO
SE
Agents
U
Clinical Association
53, 54, 55
✔
56, 57,
58, 59
57, 58, 59
✔
60, 61
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
SE
.
Agents Associated with Potential LACK OF BENEFIT
Result
ALK
FISH
Negative
ROS1
FISH
Negative
ERCC1
IHC
Positive
2+ 70%
fluorouracil,
capecitabine,
pemetrexed
TS
IHC
Positive
2+ 70%
gemcitabine
RRM1
IHC
Positive
2+ 75%
cetuximab
EGFR
IHC HScore
Negative
40
SPARC
Monoclonal
IHC
Negative
SPARC
Polyclonal
IHC
Negative
c-KIT
Next
Gen SEQ
PDGFRA
Next
Gen SEQ
c-KIT
Next
Gen SEQ
Lack of
Potential
Benefit
✔
✔
12, 13, 14
✔
17, 18,
19, 20
✔
21, 22, 23
✔
24
✔
25
0+ 100%
✔
36, 37
2+ 3%
✔
36, 37
✔
47, 48, 49
✔
50, 51, 52
✔
47, 48, 49
O
N
LY
.
N
O
S
PO
SE
R
PU
15, 16
E
Pathogenic A502_Y503dup
IV
nab-paclitaxel
Data
Reference
Level*
LI
N
Decreased
Potential
Benefit
T
cisplatin,
carboplatin
Potential
Benefit
C
crizotinib
✝
Value
AL
Method
IC
Test
FO
R
Agents
U
Clinical Association
Wild Type
Pathogenic A502_Y503dup
LU
sunitinib
ST
R
AT
imatinib
EP
O
R
T.
IL
*The level of evidence for all references is assigned according to the Literature Level of Evidence Framework consistent with the US Preventive
Services Task Force described further in the Appendix of this report. The data level of each biomarker-drug interaction is the average level
of evidence based on the body of evidence, overall clinical utility, competing biomarker interactions and tumor type from which the evidence
was gathered.
= Greater level of evidence
R
= Intermediate level of evidence
E
= Lower level of evidence
SA
M
PL
✝ Refer to Appendix for detailed Result and Value information for each biomarker, including appropriate cutoffs, unit of measure, etc.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
U
SE
.
Expanded Mutational Analysis by Next Generation Sequencing
Frequency (%)
Exon
BRAF
V600E
2
2
Result
LI
N
Alteration
Pathogenic
C
Gene
IC
AL
Genes Tested With Alterations
FO
R
Interpretation: A pathogenic variant was detected in of this sample.
LY
.
N
O
T
BRAF encodes a protein belonging to the raf/mil family of serine/threonine protein kinases. This protein plays a role in regulating the
MAP kinase/ERK signaling pathway initiated by EGFR activation, which affects cell division, differentiation, and secretion. BRAF somatic
mutations have been found in melanoma (43%), thyroid (39%), biliary tree (14%), colon (12%), and ovarian tumors (12%). Patients with
mutated BRAF genes have a reduced likelihood of response to EGFR targeted monoclonal antibodies, such as cetuximab in colorectal
cancer. A BRAF enzyme inhibitor, vemurafenib, was approved by FDA to treat unresectable or metastatic melanoma patients harboring
BRAF V600E mutations. Various clinical trials (on www.clinicaltrials.gov) investigating agents which target this gene may be available, which
include the following: NCT01543698, NCT01352273, NCT01709292.
A502_Y503dup
2
2
Pathogenic
PO
SE
Interpretation: A pathogenic variant was detected in of this sample.
S
c-KIT
O
N
BRAF inherited mutations are associated with Noonan/Cardio-Facio-Cutaneous (CFC) syndrome, syndromes associated with short stature,
distinct facial features, and potential heart/skeletal abnormalities.
IV
E
PU
R
c-Kit is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. This receptor binds to stem
cell factor (SCF, a cell growth factor). As c-Kit is a receptor tyrosine kinase, ligand binding causes receptor dimerization and initiates a
phosphorylation cascade resulting in changes in gene expression. These changes affect proliferation, apoptosis, chemotaxis and adhesion.
C-KIT mutation has been identified in various cancer types including gastrointestinal stromal tumors (GIST) (up to 85%) and melanoma
(7%). c-Kit is inhibited by multi-targeted agents including imatinib, sunitinib and sorafenib. Various clinical trials (on www.clinicaltrials.gov)
investigating agents which target this gene and/or its downstream or upstream effectors may be available for patients carrying c-KIT
mutation, which include the following: NCT01028222, NCT01092728.
AT
Germline mutations in c-KIT have been associated with multiple gastrointestinal stromal tumors (GIST) and Piebald trait.
E746_A750del
2
2
Pathogenic
R
EGFR
ST
Interpretation: A deletion was detected in this sample
E
R
EP
O
R
T.
IL
LU
EGFR or epidermal growth factor receptor, is a transmembrane receptor tyrosine kinase belonging to the ErbB family of receptors.
Upon ligand binding, the activated receptor triggers a series of intracellular pathways (Ras/MAPK, PI3K/Akt, JAK-STAT) that result in cell
proliferation, migration and adhesion. Dysregulation of EGFR through mutation leads to ligand-independent activation and constitutive
kinase activity, which results in uncontrolled growth and proliferation of many human cancers. EGFR mutations have been observed in
20-25% of non-small cell lung cancer (NSCLC), 10% of endometrial and peritoneal cancers. Somatic gain-of-function EGFR mutations,
including in-frame deletions in exon 19 or point mutations in exon 21, confer sensitivity to first-generation EGFR-targeted tyrosine kinase
inhibitors (TKIs), whereas the secondary mutation, T790M in exon 20, confers resistance to tyrosine kinase inhibitors. New agents and
novel combination therapies that include EGFR TKIs are being explored (are available (on www.clinicaltrials.gov), for primary treatment
of EGFR-mutated patients including second-generation TKIs such as icotinib (NCT01665417) for NSCLC or afatinib for advanced solid
tumors (NCT00809133) and lung neoplasms (NCT01466660). In addition, new therapies and combination therapies are being explored for
patients that have progressed on EGFR-targeted agents including afatinib (NCT01647711) for NSCLC.
SA
M
PL
Germline mutations and polymorphisms of EGFR have been associated with familial lung adeocarcinomas.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
Q209L
Frequency (%)
Exon
Result
SE
.
Alteration
Pathogenic
AL
Gene
GNA11
U
Genes Tested With Alterations
IC
Interpretation: A pathogenic variant was detected in of this sample.
HNF1A
FO
R
C
LI
N
GNA11 is a proto-oncogene that belongs to the Gq family of the G alpha family of G protein coupled receptors. Known downstream signaling
partners of GNA11 are phospholipase C beta and RhoA and activation of GNA11 induces MAPK activity. Over half of uveal melanoma
patients lacking a mutation in GNAQ exhibit somatic mutations in GNA11. Activating mutations of GNA11 have not been found in other
malignancies. Various clinical trials (on www.clinicaltrials.gov) investigating agents which target this gene may be available, which include
the following: NCT01587352, NCT01390818, NCT01143402.
Del
T
Interpretation: A deletion was detected in this sample
Pathogenic
N
LY
.
N
O
HNF1A or hepatocyte nuclear factor 1 homeobox A encodes a transcription factor that is highly expressed in the liver, found on chromosome
12. It regulates a large number of genes, including those for albumin, alpha1-antitrypsin, and fibrinogen. HNF1A has been associated with
an increased risk of pancreatic cancer. HNF1A somatic mutations are found in liver (30%), colon (15%), endometrium (11%), and ovarian
(3%) cancers. Its prognostic and predictive value is under investigation.
R132H
2
2
Pathogenic
PO
SE
Interpretation: A pathogenic variant was detected in of this sample.
S
IDH1
O
Germline mutations of HNF1A are associated with maturity-onset diabetes of the young type 3.
R
AT
IV
E
PU
R
IDH1 encodes for isocitrate dehydrogenase in cytoplasm and is found to be mutated in 60-90% of secondary gliomas, 75% of cartilaginous
tumors, 17% of thyroid tumors, 15% of cholangiocarcinoma, 12-18% of patients with acute myeloid leukemia, 5% of primary gliomas, 3%
of prostate cancer, as well as in less than 2% in paragangliomas, colorectal cancer and melanoma. Mutated IDH1 results in impaired
catalytic function of the enzyme, thus altering normal physiology of cellular respiration and metabolism. IDH1 mutation can also cause
overproduction of onco-metabolite 2-hydroxy-glutarate, which can extensively alter the methylation profile in cancer. In gliomas, IDH1
mutations are associated with lower-grade astrocytomas and oligodendrogliomas (grade II/III), as well as secondary glioblastoma. IDH
gene mutations are associated with markedly better survival in patients diagnosed with malignant astrocytoma; and clinical data support
a more aggressive surgery for IDH1 mutated patients because these individuals may be able to achieve long-term survival. In contrast,
IDH1 mutation is associated with a worse prognosis in AML. In glioblastoma, IDH1 mutation has been associated with significantly better
response to alkylating agent temozolomide. Various clinical trials (on www.clinicaltrials.gov) investigating agents which target this gene and/
or its downstream or upstream effectors may be available, which include the following: NCT01534845.
G13D
ST
KRAS
2
2
Pathogenic
LU
Interpretation: A pathogenic variant was detected in of this sample.
EP
O
R
T.
IL
KRAS or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog encodes a signaling intermediate involved in many signaling cascades
including the EGFR pathway. KRAS somatic mutations have been found in pancreatic (57%), colon (35%), lung (16%), biliary tract (28%),
and endometrial (15%) cancers. Mutations at activating hotspots are associated with resistance to EGFR tyrosine kinase inhibitors (erlotinib,
gefitinib) and monoclonal antibodies (cetuximab, panitumumab). Various clinical trials (on www.clinicaltrials.gov) investigating agents which
target this gene may be available, which include the following: NCT01248247, NCT01229150.
SA
M
PL
E
R
Several germline mutations of KRAS (V14I, T58I, and D153V amino acid substitutions) are associated with Noonan syndrome.
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
A Study of the Safety and Pharmacokinetics
of SAR245409 Tablets in Patients With Solid
Tumors or Lymphoma
1
PIK3CA
SAR245409
(XL-765)
NCT01587040
Open Label Treatment Extension Study With
SAR245408 or SAR245409 as a Monotherapy
or as a Combination Regimen
1
PIK3CA
SAR245409
(XL-765)
NCT01576666
Phase Ib, Dose Escalation Study of Oral
LDE225 in Combination With BKM120 in
Patients With Advanced Solid Tumors
1
PIK3CA
BKM120
NCT01562275
A Study Evaluating the Safety, Tolerability,
and Pharmacokinetics of GDC-0973
in Combination With GDC-0068 When
Administered in Patients With Locally
Advanced or Metastatic Solid Tumors
1
PIK3CA
NCT01553942
Afatinib With CT and RT for EGFR-Mutant
NSCLC
2
NCT01545947
Study Assessing Safety, Pharmacokinetics
and Efficacy of CC-223 With Either Erlotinib or
Oral Azacitidine in Advanced Non-Small Cell
Lung Cancer
NCT01543698
A Phase Ib/II Study of LGX818 in Combination
With MEK162 in Adult Patients With BRAF
Dependent Advanced Solid Tumors
US
US
CA, FL, MA, MN, NC,
OR, PA, TX, UT
GDC-0068
MA, MI, TN
Afatinib
MA
1
PIK3CA
CC-223
TX
1
NRAS ,
BRAF , KRAS
MEK162
MA, TX
NCT01540253
PI3K Inhibitor BKM120 and Docetaxel in
Treating Patients With Advanced Solid
Tumor That is Locally Advanced, Cannot Be
Removed By Surgery, or Metastatic
1
PIK3CA
BKM120
NY
NCT01531361
Vemurafenib and Sorafenib in Advanced
Cancer
1
BRAF
sorafenib ,
vemurafenib
TX
NCT01508104
Safety Study of BEZ235 With Everolimus in
Subjects With Advanced Solid Tumors
1|2
PIK3CA
BEZ235
OH
Trial of Erlotinib and BKM120 in Patients
With Advanced Non Small Cell Lung Cancer
Previously Sensitive to Erlotinib
1|2
PIK3CA
BKM120
FL, TN
Dose Finding Study of RAD001 (Everolimus,
Afinitor) in Combination With BEZ235 in
Patients With Advanced Solid Tumors
1
PIK3CA
BEZ235
AR, CA, MO, SC
NCT01480141
A Window of Opportunity Trial of Afatinib In
Early Stage Non-Small Cell Lung Cancer
(NSCLC)
2
EGFR
Afatinib
SC
EP
O
R
T.
IL
LU
ST
R
AT
IV
E
PU
R
PO
SE
EGFR
PL
S
O
N
LY
.
N
O
T
FO
R
NCT01596270
Locations
U
Drug(s)
AL
Potential
Target
IC
Phase
LI
N
Title
C
Protocol
SE
.
TM
Clinical Trials Connector
E
R
NCT01487265
SA
M
NCT01482156
** FINAL REPORT **
Patient: Patient Name
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences
To view the rest of the report, contact a
Caris Molecular Intelligence representative today.
(888) 979-8669
[email protected]
** FINAL REPORT **
Patient: Patient Report
TN13-111111
Physician: Ordering Physician Name
4610 South 44th Place / Phoenix, AZ 85040 / (888) 979-8669 / Fax: (866) 479-4925 / CLIA 03D1019490 / Zoran Gatalica, M.D., DSc, Medical Director
Caris MPI, Inc. d/b/a Caris Life Sciences