This document summarizes the story of Ted Taylor, a glioblastoma patient who was given a terminal diagnosis but found an effective targeted therapy called Vitrakvi after extensive research. Vitrakvi targets NTRK fusions and Ted tested positive for this biomarker. He worked with his oncologists to gain access to Vitrakvi from Canada and the US. While on Vitrakvi, Ted has experienced significant tumor shrinkage with minimal side effects compared to standard chemotherapy. He hopes to help other patients advocate for themselves to find effective targeted therapies.

1. TRKing the path to precision oncology; the NTRK story
Poul Sorensen, MD, PhD
BC Cancer Research Centre
Vancouver, BC, Canada

2. There is an increasing shift toward targeted therapy for cancer
CONFIDENTIAL 2
Chemotherapy Targeted Therapy
• In personalized medicine,
clinicians use biomarkers to
predict a patient's response
to therapy
• Patients are more likely to get
therapies with the greatest
impact with fewer side effects
• Anticancer drugs may be
highly effective in some, but
less effective in others
• Patients are exposed to the
risk of side effects

3. Personalized Oncology (Precision Oncology) -- incorporating
genomic information into treatment decision-making
EGFR
mutation
ALK1
fusion
ROS1
fusion
Checkpoint
inhibitors
erlotinib crizotinib
Genomic sequencing of
lung tumors
crizotinib
Mutation burden
pembrolizumab
nivolumab
PD-L1
atezolizumab
LungCancer
Chemotherapy
TissueBiopsy
Generic pathology
based care
Liquid biopsy and other
specialized pathology
techniques
osimertinib
EGFR resistance
mutation

4. Histomolecular entity versus molecular subtypes of a
common cancer: the ski resort analogy
• Molecular subtypes of
common cancer
Multiple pathogenetic
pathways and treatment
options
• Histomolecular entity
Single pathogenetic
pathway and dominant
treatment

5. Four Major Types of Genomic Alterations in Cancer
Single nucleotide substitutions
(including splice sites)
Small insertions/deletions*
Copy number
amplifications
Rearrangements/
fusions
T T
A A C C
G
T C
A A C C
G
Next round
of replication
G-C and A-T base pairs
deleted
Next round
of replication
A-T base pair added
• Activating Mutations in Oncogenes OR Disruptive Mutations in Tumor Suppressors
• e.g. NTRK fusions
Gene fusions: chimeric genes formed from fusion of coding sequences from
two normally separate partner genes

6. Discovery of the
ETV6-NTRK3 gene
fusion in pediatric
sarcomas

7. By microscopy, benign fibromatosis can look identical to
malignant congenital fibrosarcoma
Fibromatosis Congenital Fibrosarcoma
Could we find a cytogenetic or molecular marker to distinguish
these two entities?

8. t(12;15)(p13;q25) in congenital
fibrosarcoma
SAM
ETV6 (chr 12)
ETV6-NTRK3
kinase
NTRK3 (chr 15)
PI3K
AKT
Bcl-2
cell
survival
Ras
Erk1/2
Cyclin D1
GTP
Cell growth
and division

9. Ectopic expression of ETV6-NTRK3 transforms mouse fibroblasts
1. Changes in cell
appearance
2. Ability to grow without
attachment to
underlying tissues
(soft agar colony
formation)
3. Cells tumorigenic in
nude mice
Control ETV6-NTRK3
D. Wai et al, Oncogene 2000
Control ETV6-NTRK3

10. Mammary-analogue secretory
carcinoma (MASC) of salivary glands
Photomicrograph courtesy of Dr. Ken Berean
Human secretory breast carcinoma
ETV6-NTRK3 is a pathognomonic biomarker in both diseases, despite different histologies and anatomic locations

11. Hyperplasia Tumors in other mammary glands
DCIS?
Tumor focus
Tognon et al, Cancer Cell, 2002; Li et al, Cancer Cell, 2007
Human secretory breast carcinoma
Tognon et al, Cancer Cell, 2002
Breast cancer in Etv6-NTRK3
knockin mouse
Li et al, Cancer Cell, 2007
Proof of the oncogenicity of ETV6-NTRK3: different features of secretory
breast carcinomas arising in the same ETV6-NTRK3 mouse model

12. Normal physiological functions of NTRK1/2/3 (TRKA, B, and C)
PLCy
MAPK PI3K
Pain
Thermoregulation
Movement
Memory
Appetite
Metabolic homeostasis
Proprioception
NGF/
NT3
BDNF
/
NT4
NT3
Ligand binding domain
Kinase domain
Ligand dependent phosphorylation P P
NTRK1/2/3
gene
TRKA/B/C
protein
P P

13. The advent of next generation sequencing has identified numerous other gene fusion
variants involving all three NTRK genes, and across multiple tumor types
Vaishnavi A, et al. Cancer Discov. 2015;5:25-34.
Drilon A, et al. N Engl J Med. 2018;378:731-739.

14. - LMNA-NTRK1 oncogenic fusion in a soft tissue sarcoma in 41 yo female

15. NTRK fusions involve many different partner genes and in
different diseases with high clinical unmet need
Adult Pediatric/Young adult
Papillary thyroid cancer3,4
• NTRK1 fusion frequency: 11.8%
• ETV6-NTRK3 fusion frequency
(post-Chernobyl): 14.5%
Intrahepatic cholangiocarcinoma6
• NTRK1 fusion frequency: 3.6%
Glioblastoma multiforme1
• NTRK1 fusion frequency: 1%
Secretory breast cancer5
• NTRK3 fusion frequency: 92%
Mammary analogue secretory cancer2
• NTRK3 fusion frequency: >90%
Pilocytic astrocytoma8
• NTRK2 fusion frequency: 3.1%
Pediatric high-grade glioma7
• NTRK1/2/3 fusion frequency: 10%
Congenital fibrosarcoma9,10
• NTRK3 fusion frequency: 91–100%
Congenital mesoblastic nephroma (cellular
subtype)10-11
• NTRK3 fusion frequency: 83–92%
NTRK gene fusion frequencies reported from isolated case reports which used variable methodologies to detect these
genetic alterations

16. • NTRK1-3 fusions associated with many different human
cancers
– At least 25 different tumor types, including breast
cancer, ovarian cancer, colorectal cancer, melanoma,
and lung cancer
– Implicated in up to 1% of all solid tumor malignancies
– NTRK gene fusions result from gene translocation
events
• Result in overexpression and constitutive ligand-
independent activation of NTRK kinase domains
All three NTRK genes implicated in oncogenic fusions
• Suggested the possibility of targeting all
3 NTRKs with the same drug

17. Miracle in the Making
Ted Taylor GBM Survivor

18. The Diagnosis
• ER 2x Severe
Headaches
• Dr. 1x
• Final ER insist
• Receiving the news
• Surgeon next day
• Surgery 6 days
later Oct 31, 2018
• Research begins!
• Sat down Nov. 26,
2018 News

19. Research Vitrakvi
• Began research discovered 1%
• Brought Vitrakvi to my Oncologists
• Not available in Canada but step 1 was that I
needed genetic testing.
• Foundation One Cambridge, Massachusetts
• Result verification needed fore & background.
• Oncologist & Pharmacist application to Health
Canada

20. Approval Process
• Health Canada approval Special Access
Program as an initial patient for Larotrectinib
• Bayer required the Foundation One report
• Bayer approval
• Shipped from UK to Germany to Vancouver
and awaited shipment at the pharmacy
• Began taking capsule on Good Friday 2019

21. Hope
• Efficacy 75 22 Complete initial
response
• Nothing like this ever before
• TMZ largest breakthrough in 15
years - weeks
• Standard of Care 14.6 months for
my median survival with all
achievements in human history.
• In most cases optimal treatment,
patients have a median survival of
less than one year, there is no cure
and a high rate of recurrence.
Only 25% of patients survive more
than one year. The U.S. National
Center for Biotechnology
Information (NCBI) lists long term
survival beyond three years limited
to less than 2% of patients. 98%
chance you do not make it.

22. Side Effects & Adjustments
• Take Vitrakvi 2x per day
with breakfast and
dinner daily.
• Side effects Increased
liver enzymes AST & ALT
• Liver enzymes – my
research (In trials some
had to stop – be your
own best advocate)
• Water intake, 3L,4L,5L
adjustments, Bilirubin's

23. ALT
Before Adjusting Water and
Bilirubin’s graph is Parabolic

24. AST
After Adjustments Normal range or
slightly above – Be your own best
advocate.

25. Side Effects & Adjustments
• Juxtapose against Standard of Care. TMZ reaction & immune,
Red, White, Platlets. 6x Platlet Transfusions. Radiation 60 gy.
Was told 100% I would lose my hearing in right ear. Increase
radius of additional 2.5cm Fatigue, stamina, memory
Not the same person but blessed to
be alive and kept calm, friendly
personality.

26. Liquid vs.
Capsule
• April 19, 2019 started Capsule Vitrakvi
• September 07, 2019 started liquid. (Health
Canada approval July 31, 2019; but, approval
was only for the liquid version).
• Purpose dose vs. practical impact for adults
• Worked with Health Canada to work towards
capsules being approved. Back to capsules
December 2020.

27. Scans & Results
• Scans and results
- Midline shift. Tumor location shrinking
• Personal Impact on
me – save
• Comparison

28. . . .

29. 1% and the Future
• 1%
• 100 people watching
• How many doctors watching with how many
patients with any solid form cancers?
• Future of medicine get tested. No matter how
up to date your oncologists and doctors are
they simply cannot know every new drug or
treatment. Research and become your own
best advocate. Work with receptive oncologist

30. Personal Impact
• What Can I do?
• Be your own best advocate
• I want to help others.
• Keto, Boswellia-Dex,
• Hyperthermia
• Exercise
• Stay at peace
• Relax time, walks, family & friends
• Quiet time

31. Glioblastoma Guide
www.glioblastomaguide.com
YouTube Channel: Glioblastoma Guide

32. Thank You
My Oncologists, Pharmacist,
Surgeon, support of my family,
friends, and all those who
helped make Vitrakvi possible
which is part of my
“Miracle in the Making”

33. Canadian Cancer Survivor Network
Contact Info
1750 Courtwood Crescent, Suite 210
Ottawa, ON K2C 2B5
Telephone / Téléphone : 613-898-1871
E-mail: jmanthorne@survivornet.ca or info@survivornet.ca
Website: www.survivornet.ca
Twitter: @survivornetca
Facebook: www.facebook.com/CanadianSurvivorNet
Instagram: @survivornet_ca
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