Tempus xT - Primary test in cancer space

Question 1

What is the test most often ordered by clinicans and considered the “Core” of Tepus Oncology tests?

Answer 1

xT

Question 2

Why was it designed?

Answer 2

-To help modernize cancer care to give their patients the best options.

Question 3

Components of the test:

Answer 3

• Tumor+normal match DNA sequencing
• Transcriptome-based RNA sequencing
• Optional IHC analysis of PD-L1 and MMR
• Structured clinical data included

Question 4

xT allows clinicians to gain insight to a patient’s tumor, true or false?

Answer 4

True

Question 5

There are two categories of information that xT generates, what are these?

Answer 5

1. ) Therapeutically relevant infromation

2. ) Clinical trial matching

Question 6

What does the therapeutically relevant information show?

Answer 6

• Somatic DNA variants
• Somatic RNA fusions and rearrangements
• Immunotherapy metrics
• Incidental germline findings

Question 7

What about the clinical trail matching information?

Answer 7

• Combines molecular and clinical data

- TIME trial

Question 8

Somatic mutations

Answer 8

occur in a single body cell and cannot be inherited.

Question 9

Germline mutations

Answer 9

occur in gametes and can be passed onto offspring. Aka- every cell in the entire organism will be affected.

Question 10

Are there add-ons for the test that a clinician can choose to opt-in for?

Answer 10

Yes. There is a section under the “testing options” where add-on tests can be checked.

Question 11

What is NOT an element of the test?

Answer 11

optional FISH findings

Question 12

Is the “normal match” required for Tempus to perform the test?

Answer 12

No - it’s just encouraged.

Question 13

What is a tumor “Normal match”?

Answer 13

Comparing the DNA of the tumor to a patient’s “normal DNA” their “germline DNA”. Looking to see what variants are exclusive to the tumor and which are normal to that specific patient’s DNA. Sequencing them both at the same time and comparing them to each other.

Question 14

When sequencing the tumor, what factors are we looking for?

Answer 14

1. ) Genes
2. ) Depth of Coverage
3. ) Alterations Reported
4. ) Immunotherapy Metrics
5. ) Specimen Requirements
6. ) Tumor content

Question 15

How many genes do we sequence for the xT tumor sequencing?

Answer 15

648

Question 16

What’s the depth of coverage?

Answer 16

500x

Question 17

what alterations are reported?

Answer 17

Somatic SNV’s (somatic point mutations found in cancer tissue) / Indels CNV’s (copy # variations)

Question 18

what alterations are reported?

Answer 18

Somatic SNV’s / Indels / CNV’s

Question 19

what specimen requirements?

Answer 19

• Solid tumor: FFPE block + 1 H&E slide
• 10 FFPE slides+ 1 H&E slide
• 1 mL bone marrow
• 8 mL peripheral blood

Question 20

what is the tumor content percent we need present in the specimen?

Answer 20

20% must be the tumor

Question 21

how many genes?

Answer 21

648 sequenced, incidental germline findings reported out for 65.

Question 22

Depth of coverage?

Answer 22

150x

Question 23

alterations reported?

Answer 23

Incidental germline pathogenic/ likely pathogenic SNV’s, indels.

Question 24

immunotherapy metrics?

Answer 24

N/A

Question 25

Specimen requirements?

Answer 25

Solid tumor: 8mL blood OR 650 uL salvia
Lymphoma: Saliva
Leukemia: No normal match

Question 26

Tumor content needed?

Answer 26

No tumor content needed since this is “normal DNA”

Question 27

The normal match is not required but is strongly preferred. True or false?

Answer 27

True

Question 28

why is this?

Answer 28

because the normal match allows the tumor DNA to be compared against the patient’s own normal DNA instead of a reference genome.

Question 29

Does the normal match DNA improve the accuracy by reducing somatic false-positive variant’s?

Answer 29

Yes

Question 30

Why does Tumor-Normal match matter?

Answer 30

• accurate somatic mutation reporting and cancer therapy matching.
• identification of provenance errors
• more accurate reporting of tumor metrics.

Question 31

approx 0.2-3.5% of the time, the tumor specimen is not from the intended patient. True or false?

Answer 31

True

Question 32

During tumor-only tests, what is the tumor being compared against?

Answer 32

A reference genome.

Question 33

what about in the tumor-normal? what is that being compared against?

Answer 33

A patient’s germline DNA

Question 34

Would we list a germline variant that came through on a test as a “somatic variant” on a clinical report?

Answer 34

No. Not on a “tumor-normal” test but we would on a “tumor-only” test.

Question 35

Facts about normal match:

Answer 35

• not required but we do encourage it
• can be blood or saliva
• if it’s blood, it can be in a streck tube

Question 36

Why does the streck tube have an advantage?

Answer 36

Because it can be converted to a liquid biopsy without submitting in more samples.

Question 37

what does that mean in relevance to testing?

Answer 37

Streck tube is preferred due to the easy conversion to xF assay (liquid biopsy) if needed.

Question 38

What immunotherapy metrics are automatically included?

Answer 38

TMB and MSI

Question 39

TMB

Answer 39

Tumor Mutational Burden- Important marker for determining if a patient is a candidate for Immunotherapy.

Question 40

MSI

Answer 40

Microsatellite Instability

Question 41

what’s important about the TMB

Answer 41

• No additional sample is needed
• Reported as high if measured as 10 or greater
• Off-label indication for pembrolizumab (?)

Question 42

What about MSI?

Answer 42

• No additional sample needed but tumor must be >30%
• Reported as high, equivocal, or stable
• On-label indication for pembrolizumab