A comprehensive and reliable solution to enhance personalized cancer care

FOLLOW ITLiquid Biopsy Cancer Hotspot Panel

Information for Medical Professionals

®

INTRODUCING: THE FOLLOW IT CANCER HOTSPOT PANELA cell-free circulating tumor DNA assay for the detection of somatic cancer mutations in mutiple solid tumor types.FOLLOW IT is a liquid biopsy test that analyzes cell-free circulating tumor DNA (ctDNA) in the plasma isolated from peripheral blood.  This minimally invasive assay is suitable for individuals with solid tumors. FOLLOW IT may help enhance care by monitoring disease without the risks or costs associated with painful repeat biopsies.   

TESTING INDICATIONS FOR FOLLOW IT

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WHO SHOULD HAVE FOLLOW IT?FOLLOW IT is beneficial when there is:

Detecting mutations that have prognostic, diagnostic or

therapeutic value when there is insufficient or unavailable

tissue for genomic profiling

Understanding the molecular cause of resistance to

current therapy in real time hence potentially guiding 

therapy choices

Monitoring targetable mutations that are detectable

by repeat testing

Suspected or known relapsed disease

where ctDNA testing can detect resistance mutations

Metastatic diseasewhere ctDNA testing can track therapy response

dynamically

Unavailable biopsy, or tissue that is

insufficient or exhausted 

Poor quality DNA from biopsied tissue causing

molecular test failure

FOCUSED ON ACTIONABLE RESULTS30 cancer-associated genes, 23 exons and 146 hotspots.

The FOLLOW IT panel maximizes treatment options by:• Focusing on clinically actionable sensitizing and resistance mutations within a carefully selected set of hotspots.• Keeping the panel small, focused and robust also provides a cost-effective solution.

Gene Content & Associated Treatment Options Genes and Associated Cancers

Gene

KeyOn-Label Drugs O�-Label Drugs Clinical Trial Resistance

Position TherapeuticOptions

AKT1ALKARBRAFCTNNB1DDR2EGFRERBB2ESR1GNA11GNAQGNASHRASIDH1IDH2KITKRASMAP2K1(MEK1)MAP2K2(MEK2)METNRASPDGFRAPIK3CAPOLEPTCH1PTENRETROS1SMOTP53

E17

T1151, L1152, C1156, F1174, L1196, L1198, G1202, 01203, S1206, G1269, R1275

L702H, S741, W742, V716, H875, F877, T878

Q201, G466, F468, G469, Y472, D594, G596, L597, V600, K601

D32, S33, G34, S37, T41, S45

L239, 1638, S768

S492, Exon18, Exon19, Exon20, Exon21

G309, S310, L755, C805, Exon20

K303, S463, V534, P535, L536, Y537, D538

Q209

Q209

R201

G12, G13, Q61

R132

R140, R172

Exon9, Exon11, Exon13, T670, D816, D820, N822, Y823, A829

G12, G13, A59, Q61, K117, A146

Q56, K57, K59, D67, C121, P124, P387

F57, Q60, K61, L119

Y1253, Exon13, Exon14 (-50 to +25), Exon18

G12, G13, A59, Q61, K117, A146

N659, R560-E571, D842, L839-Y849

R88, E542, E545, Q546, D549, M1043, N1044, A1046, H1047, G1049

Exon9, Exon10, Exon11, Exon12, Exon13, Exon14

W844, G1093

R130

C634, V804, M918

L2026, G2032

D473, S533, W535

Exon4, Exon5, Exon6, Exon7, Exon8, Exon9

Cancer Associated Genes

Basal Cell CarcinomaBladder CancerBreast CancerColorectal CancerEndometrial CancerGISTGliomaHead and Neck CancerLung CancerMelanomaNeuroblastomaOvarian CancerPancreatic CancerProstate CancerThymic CancerThyroid Cancer

PTCH1, SMO

HRAS, PIK3CA

AKT1, BRAF, DDR2, ERBB2 (HER2), ESR1, PIK3CA, PTEN

AKT1, BRAF, CTNNB1, EGFR, KRAS, MET, NRAS, PIK3CA, PTEN, POLE

CTNNB1, DDR2, PIK3CA, PTEN, POLE

BRAF, KIT, PDGFRA

BRAF, EGFR, IDH1, IDH2, PIK3CA, PTEN, SMO

BRAF, DDR2, PIK3CA

AKT1, ALK, BRAF, DDR2, EGFR, ERBB2, KRAS, MAP2K1, MET, NRAS, PIK3CA, PTEN, ROS1

BRAF, CTNNB1, GNA11, GNAQ, KIT, MAP2K1, NRAS

ALK

BRAF, CTNNB1, KRAS, NRAS, PIK3CA, PTEN

CTNNB1, KRAS

AR, DDR2, KRAS, PTEN

KIT

BRAF, CTNNB1, HRAS, KRAS, NRAS, TER

Please note: The genes on the panel are under continuous review and are subject to change. The therapeutic options are under continuous review by the FDA, NCCN and other literature and are subject to change.

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Unlike larger panels, the FOLLOW IT panel is focused on gene mutations that you can tackle through current FDA approved therapies.

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Indication

Non-Small Cell Lung Cancer

Melanoma

Colorectal Cancer

GIST

Basal Cell

Breast Cancer

Endometrial

Biomarker

EGFR exon 19 deletions and EGFR exon 21 L858R alterations (Afatinib also approved for L861Q, G719X, and/or S768I)

EGFR exon 20 resistance T790M alterations and first line in common L858R and exon 19 del

BRAF V600E 

MET exon 14 skipping

BRAF V600E 

BRAF V600E or V600K 

KRAS wild type 

KRAS and NRAS wild-type 

POLE

KIT, PDGFRA

PTCH1

PIK3CA

POLE

FDA- approved therapy

Giotrif® (afatinib), Iressa® (gefitinib), or Tarceva® (erlotinib)Vizimpro® (dacomitinib) - specific to exon 19 del or exon 21 L858R variants

Tagrisso® (osimertinib)

Tafinlar® (dabrafenib) in combination with Mekinist® (trametinib)

Xalkori®(Crizotinib)

Tafinlar® (dabrafenib) or Zelboraf® (vemurafenib)

Mekinist® (trametinib) or Cotellic® (cobimetinib) in combination with Zelboraf® (vemurafenib) Braftovi (encorafenib) + Mektovi (binimetinib) when V600E or V600K + and unresectable/metastatic melanoma

Erbitux® (cetuximab)

Vectibix® (panitumumab)

Immunotherapy

Gleevec® (imatinib)Sutent® (sunitinib)Stivarga® (regorafenib)

Vismodegib® (erivedge)Odomzo® (sonidegib)

Piqray® (Alpelisib)

Immunotherapy

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COST EFFECTIVE FOR PATIENTS AND HEALTHCARE DECISION-MAKERSFOLLOW IT is the most cost-e�ective ctDNA available in the market.

ACCURATE AND ROBUST GENOME ANALYTICSA state-of-the-art bioinformatics and reporting platform.

EASE OF MONITORING

FOLLOW IT has been designed to allow for ease of coverage and reimbursement by the centers of Medicare and Medicaid services (CMS) according to their current rates for somatic mutation testing

This advantage ensures patients will have access to up to date personalized therapies for cancer while minimizing any potential financial burden

FOLLOW IT is less invasive when compared to tissue biopsy and offers better patient experience

FOLLOW IT can be used as often as necessary to monitor the patient’s progress

• The FOLLOW IT assay is supported by a robust, accurateand high-throughput bioinformatics system, the ContextualGenomics Informatics and Reporting Platform for accurateidentification of mutations.

• The central component of this system is a proprietarybioinformatics and genome analytics pipeline. The pipelinehas been built on state-of-the-art computational algorithmsand has been rigorously validated.

• The pipeline has consistently demonstrated high accuracywith sensitivity and specificity greater than 99%.

TIMELY RESULTS 5-day turnaround time from sample receipt to report generation allows fast clinical action.

• FOLLOW IT assay results are issued to the oncologist within 5 days of the sample being received in the laboratory. This rapid turnaroundtime allows oncologists to implement effective treatment plans within a meaningful timeframe that could have a significant impact on apatient’s clinical outcome.

• The FOLLOW IT assay secures patient privacy since the library preparation, sequencing, report issuing and sign-off take place on thelaboratory’s computer and local servers.

5-DAY TURNAROUND TIME WORKFLOW

Patient Sample

DNA Extraction

Multiplex PCR

Library Preparation & Sequencing

Bioinformatics Expert Interpetations/ Clinical Trials Database

+

0 5Local Laboratory

Local Computer Local Computer

Cloud Based Services

Report Oncologist

Collection of peripheral blood

from patient

DNA extracted from plasma

Enrichment for mutational hotspot

regions of interest in 30 carefully chosen

cancer genes

Construct library, prepare template

& run NGS

Perform data analysis and

variant calling

Experts review mutation results & match them with approved drugs.

They will also identify any available relevant clinical trials adapted for health jurisdiction

Report is issued & delivered to the oncologist on the 5th day. The

physician report is accompanied by a short patient report

PATIENT INFORMATION NEVER LEAVES THE LOCAL SERVERS

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QUALITY CONTROL & ASSURANCE Contextual Genomics ensures accuracy and quality control of the FOLLOW IT assay through a set of quality assurance methods utilizing DNA sequence barcodes known as QUALITY NEXUS™.QUALITY NEXUS is incorporated into the assay and bioinformatics pipeline. 

QUALITY NEXUS• Improves the signal to noise ratio, enabling detection of mutations at significantly lower VAF.• Reduces the potential for false outcomes from the assay which will ultimately benefit the health outcomes of cancer patients.

COMPREHENSIVE AND INFORMATIVE REPORTSContextual Genomics’ reports allow oncologists to make more informed treatment decisions.

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A summary of the results indicating whether mutations are present or not with therapeutic recommendations based on the gene mutation and the patient profile in addition to the number of clinical trials available.

• Clinical trials are carefully curated by experts using specific trial eligibility criteria including tumor molecular profile, organ and histological type.

• The Reporting System automatically matches open and curated clinical trials to a patient’s clinical profile based on the presence or absence of gene mutations, tumor type, histological type and availability of the trial in the country of the laboratory’s jurisdiction.

• The clinical trials are reviewed and selected by a certifiedclinical molecular geneticist.

Patient Name:Report ID: 544

Date of Birth: NoneSurgical ID:

Patient ID: pt-DNA-10599-CG001QV40Run26-22Panel: Full

FOLLOW IT Report®

CLINICAL TRIALS

TABLE 3: The clinical trials included in the report are sourced from clinicaltrials.gov. We select trials based on tumour histotype and mutation status, with a speci�c focus on trials of targeted therapy. The inclusion of a trial in our report does not necessarily mean that the patient would be eligible. Patients’ eligibility for a trial, and the bene�t that they may derive from it, will depend on additional factors that must be assessed by the oncologist. Conversely, the list of potentially relevant trials in our report may not be complete. We may have overlooked relevant trials on these websites, or there may be relevant trials listed elsewhere. Please let us know if you identify a trial of targeted therapy that could have been included in a patient’s report.

STUDY GENES PHASE COUNTRIES TITLE

NCT02912572 Phase 2United states of America

A Phase 2, Two-Group, Two-Stage, Open-Label Study of Avelumab (MSB0010718C) in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer

PATIENT INFORMATION

Patient Name: Jane Doe Date of Birth: 11/05/1957 Sex: FemaleCare Card #: 010101 Province of issue: BC Diagnosis: None Reason for Referral: Diagnostic Evaluation Previous Molecular Tests: N/A Test Requested: FOLLOW IT Date of Receipt: None Date of Report: 2019-08-02 11:41:22

HEALTHCARE PROVIDER INFORMATION

Referring Physician: Nathaneal DownInstitution: ABC General Hospital Address: Phone: (999) 000-999 Fax: Pathologist: Nigel Nigel Institution: ABC General HospitalAddress: Phone: (999) 000-999 Fax:

SPECIMEN INFORMATION

Specimen Collection Date: None Specimen Source: BloodSpecimen Type: Plasma Primary Site of Tumour: Endometrium Histologic Type: Endometrioid carcinomaSample: DNA-10599-CG001QV40Run26-22

CONSIDERATIONS

SUMMARY OF TEST RESULTS

Key Mutations Present*

Gene cDNAchange

AminoAcid

ChangeExon

AllelicRatio(%)

Therapeutic Implication Level of EvidenceClinicalTrials

Available

POLE

c.1231G>T(NM_006231.3)

V411L 13 19.4

Tier: II.D• Literature

0Tier: II.D• Literature

PIK3CAc.263G>A(NM_006218.3)

R88Q 2 28.1Tier: II.D• Literature

0

PTENc.389G>A(NM_000314.6)

R130Q 5 24.9 Tier: II.D• Literature

0

TP53c.638G>A(NM_000546.5)

R213Q 6 3.1 NA (see other �ndings section) NA NA

TABLE 1: Mutations Present

- POLE mutations are associated with an ultra-mutated tumour phenotype and an excellent prognosis in endometrioid endometrial carcinoma.- May respond to immunotherapy in the rare recurrent/metastatic setting.- PIK3CA and PTEN mutations: In the context of POLE-mutated endometrioid endometrial carcinoma, PIK3CA and PTEN mutations are considered secondary events and are not currently associated with prognostic or therapeutic signi�cance.

Patient Name:Report ID: 544

Date of Birth: NoneSurgical ID:

Patient ID: pt-DNA-10599-CG001QV40Run26-22Panel: Full

FOLLOW IT Report®

Associated with an excellent prognosis in endometrioid endometrial carcinoma

May respond to immunotherapy in the rarerecurrent/metastatic setting

Alterations in PIK3CA are frequent (70%) in POLE- mutated endometrial carcinoma are considered secondary events and are not currently associated with prognostic or therapeutic signi�cance.

Alterations in PTEN are frequent (94%) in POLE- mutated endometrial carcinoma and are considered secondary events and are not currently associated with prognostic or therapeutic signi�cance.

This test is an amplicon based hotspot next-generation sequencing assay (NGS) that interrogates clinically actionable gene alteration incirculation tumour DNA extracted from plasma. The test results, interpretations and clinical trials included in this report are provided in thecontext of a primary cancer type as reported by the referring physician.

WHY CHOOSE FOLLOW IT?

FOCUSED ON ACTIONABLE RESULTS

FOLLOW IT is designed to reduce ambiguity in results and improve clinical management through targeting only actionable mutations

FAST TURNAROUND TIME

A complete sample-to-report service within 5 working days, permitting timely action

COMPREHENSIVE REPORT Reports include detailed, accurate interpretation and current treatment options based on the molecular profile of the tumor. It also provides links to a list of currently available clinical trials

COST-EFFECTIVE FOLLOW IT is the most cost effective ctDNA test in the market. This reduces financial burden on healthcare providers and patients

MINIMALLY INVASIVEThe assay removes the need for costly and painful biopsies

ACCREDITATION All Contextual Genomics’ assays were developed under full accreditation of the CAP and CLIA

Genes

Hotspots

Exons

Turnaround Time (TAT)

Mutation types

Sensitivity

Specificity

Assay Cutoff

Mean Depth of Coverage

Assay Reproducibility

Sample Type

Sample Requirement

30

146

23

5 days

SNVs, deletions and insertions (up to 24bp)

>99%

>99%

Below 1% VAF

8500x

100%

Blood

2 x 10 mL of blood in Streck tubes

OUR STORY:Contextual Genomics is founded and led by world leaders in oncology, genomics and bioinformatics to develop and deliver high quality and affordable genomic-based molecular diagnostics to cancer patients worldwide. We provide turn key solutions to clinical laboratories that combine broad scientific and medical expertise, patented innovation, and cutting-edge information and software technologies to empower them to lead the shift in precision oncology that bring about better patient diagnosis and treatment.

Suite 204 - 2389 Health Sciences MallVancouver, BC, Canada V6T 1Z3

www.contextualgenomics.com

©Copyright 2020 Contextual Genomics. FOLLOW IT is a trademark of Contextual Genomics. All other trademarks are the property of their respective owners. Subject to change without notice.

IMPROVED THERAPEUTIC PRECISION &

BETTER TREATMENT OUTCOMES FOR PATIENTS

FOLLOW IT TECHNICAL SPECIFICATIONS

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