P E R S O N A L I S AT I O N O F M O L E C U L A R

P R O F I L I N G A C C O R D I N G T O T U M O U R T Y P E

Package Plus

EX PAN DING M OLECULAR TUM OUR PROFILING: NGS AND BEYOND

• Immunohistochemistry markers

• RNA fusions (incl. NTRK, etc.)

• Solid and blood molecular profiling

• Microsatellite instability

Because combining different molecular profiling assays is the key to maximising the clinical benefit of the treatment, OncoDNA automatically adds additional tests adapted to each tumour type to all NGS solid biopsies analysis, called “PACKAGE PLUS” (1)

edit ion2020

CASE REPORT #1According to each tumour type, OncoDNA perform a specific

set of Immunohistochemistry analyses to fine tune the clinical

relevance of the NGS sequencing.

Therefore, OncoDNA, in addition to the sequencing of 313 genes, automatically adds a unique combination of molecular tests (such as IHCs,

methylation, etc.) – what we call “PACKAGE PLUS”.

The 2020 Package Plus is performed for all OncoDEEP and OncoSTRAT&GO analyses.

It includes now:

• specific tests of immunohistochemistry (IHC) for chemo, immuno and targeted therapies,

• other molecular tests like MSI and Fusions for immuno and targeted therapies

1,057 patients in 30 countries (4 continents) were treated

by oncologists using OncoDNA’s Molecular Profiling &

Information Services.

For 92% of the oncologists, combining NGS with Package Plus

data results created a better clinical insight. (1)

Patients� with� treatment� options� (approved� for� the� cancer� type� analysed,�approved� for� other� cancer� types� or� under� development)� and� without�treatment�options,�according�to�test.

IMPORTANT�FOR�CUP:�Always�clearly�state�“CUP”�when�ordering�your�analysis�(never�“unknown”�or�other�wording).�This�is�to�ensure�we�perform�the�most�suitable�analysis).

Based on the Package Plus analysis, this patient should be sensitive

to taxane, topoisomerase I and II inhibitors, gemcitabine-based

chemotherapies and to PD-1/PD-L1 inhibitors. The immunogram

shows a high potential response to immunotherapy.

Therefore, based on the level of CD8+ lymphocytes and PD-L1

expression, treatment based on PD-1/PD-L1 inhibitors could be

associated with a potential clinical benefit for this patient. On the

other hand, this patient is not thought to be sensitive to platinum

salt, 5-FU-based chemotherapies.

We provide microsatellite instability (MSI) testing for better

immunotherapy selection.

• Hormonal receptors,

• CD8 T cell infiltration,

• PD-L1 expression,

• HER2,

• PTEN,

• ...

These are only a few examples of the multiple targets that the

Package Plus assesses.

Carcinoma of Unknown Primary, Stage IV

Female, 42 years old

TU M O U R S PE C I FI C M A R K E R S

Because you always need specific IHC

Because NGS alone is not enough for a decision for treatment

MSI- Because DNA Hypermutability is key

PD-L1

TMB

CD8

MSI

MUT SENSI

PE R S O N A LI SATI O N O F TU M O U R PRO FI LI N G ACCO R D I N G TO E AC H TU M O U R

T Y PE I S K E Y TO I M P ROV E D C LI N I C A L B E N E FIT S

NGS only Package Plus and NGS

Without treatment

With therapeutic alternative

73%

8%

92%

27%

ctDNA DNA of PBMCs

CASE REPORT #2

• In OncoSTRAT&GO, NTRK fusion is analysed at the RNA level for all tumour types

• In OncoDEEP, NTRK RNA fusion is analysed for 5 tumour types: NSCLC, bladder (urothelial) cancer, cholangiocarcinoma, thyroid cancer and

paediatric glioblastoma. For other tumours, NTRK IHC is performed, and, if the result is positive, the oncologist is informed and, depending

on his/her needs for fusion partners for drug market access, the Fusion Panel is performed.

(For your convenience, no NTRK Stand Alone analysis is needed, it is always included in Package Plus)

According to the tumour type with OncoSTRAT&GO we focus either on the circulating tumour DNA (for deciphering tumour heterogeneity) or on

DNA from blood cells (for studying specific germline gene alterations related to BRCAness phenotype that are challenging to detect in FFPE samples).

In its new 2020 Package Plus OncoDNA uses a specific RNA Fusion Panel*

to detect EGFRvIII and MET exon 14 skipping events along with major

ALK, BRAF, FGFR, NRG1, NTRK, RET, and ROS1 fusions and selects point

mutations in 14 key gene targets. (2-8)

*The� Fusion� Panel� is� performed� with� OncoDEEP� for� 5� tumour� types:� NSCLC,� bladder�(urothelial)�cancer,�cholangiocarcinoma,�thyroid�cancer�and�paediatric�glioblastoma.�When�using�OncoSTRAT&GO�the�fusion�panel�is�applied�for�all�tumour�types. Patient progressing on Cisplatin + Gemcitabine

combined with Sorafenib TK inhibitor.

Package Plus shows the presence of FGFR3 fusion. This

patient should be sensitive to FGFR fusion TK inhibitors

(Pemigatinib, Derazantinib or Infigratinib).

Cholangiocarcinoma, Stage IV

Male, 65 years old

NTR K 1 , 2 A N D 3 – I H C O R R NA FU S I O N D E TE C TI O N

PE R S O N A LI S E D B LO O D A NA LYS I S D E PE N D I N G O N TU M O U R T YPE

A H I G H PE R FO R M I N G FU S I O N A NA LYS I S

More than a 75% response rate when targeting NTRK fusion-positive tumors using NTRK inhibitor (9)

OncoSTRAT&GO is an integrated approach that combines the analyses of a solid biopsy with the analysis of a blood biopsy.

GENE TARGETS

ALK BRAF EGFR FGFR1 FGFR2

FGFR3 KRAS MET NRG1 NTRK1

NTRK2 NTRK3 RET ROS1

In 86% of metastatic patients, solid and liquid

biopsies provide different information on

genetic alterations (10)

Inherited exon deletions/duplications leading

to BRCAness phenotype are difficult to detect

in FFPE biopsies (DNA degraded)

RECOMMENDED FOR :

the following stage IV solid tumours in adults: non-small cell lung cancer,

breast cancer (HR+ and HER2+), colorectal cancer, cancer of unknown

primary.

RECOMMENDED FOR :

the following stage IV solid tumours in adults: breast cancer (TNBC),

ovarian cancer, pancreatic cancer, prostate cancer.

Gene 2

Gene 2

Gene 1

+ >Gene 1

(1) �Laes�et�al.�The�clinical�impact�of�using�complex�molecular�profiling�strategies�in�routine�oncology�practice;�Oncotarget,�Vol.�9,�(No.�29),�pages�20282-20293�(2018)

(2)�Barerca�et�al.�Anaplastic�lymphoma�kinase�in�human�cancer.�J�Mol�Endocrinol.�2011�Jul�4;47(1):R11-23.

(3) Maraka�S�et�al.;�BRAF�alterations�in�primary�brain�tumors.�Discov�Med.�2018�Aug;26(141):51-60.

(4) Kheder�ES�et�al.;�Emerging�Targeted�Therapy�for�Tumors�with�NTRK�Fusion�Proteins.�Clin�Cancer�Res.�2018�Dec�1;24(23):5807-5814

(5) Offin�M.�et�al.;�Acquired�ALK�and�RET�Gene�Fusions�as�Mechanisms�of�Resistance�to�Osimertinib�in�EGFR-Mutant�Lung�Cancers.�JCO�Precis�Oncol.�2018;2.�doi:�10.1200/PO.18.00126.

(6)�Mendoza�L.;�Clinical�development�of�RET�inhibitors�in�RET-rearranged�non-small�cell�lung�cancer:�Update.�Oncol�Rev.�2018�Jul�10;12(2):352

(7)��Davare�MA�et�al.;�Rare�but�Recurrent�ROS1�Fusions�Resulting�From�Chromosome�6q22�Microdeletions�are�Targetable�Oncogenes�in�Glioma.�Clin�Cancer�Res.�2018�Dec�15;24(24):6471-6482

(8) �Qin�A.�et�al.;�Detection�of�Known�and�Novel�FGFR�Fusions�in�Non-Small�Cell�Lung�Cancer�by�Comprehensive�Genomic�Profiling.�J�Thorac�Oncol.�2019�Jan;14(1):54-62

(9) �Finzel�A.�et�al.�The�combined�analysis�of�solid�and�liquid�biopsies�provides�additional�clinical�information�to�improve�patient�care.�J�Cancer�Metastasis�Treat.�4:21�(2018)

(10) Cocco�et�al.�NTRK�fusion-positive�cancers�and�TRK�inhibitor�therapy;�Nature�Reviews�Clinical�Oncology,�Vol.�15,�pages�731–747�(2018)

REF EREN CES

PACKAGEPLUS-HQ-20200423-V1

Support from our Scientific and Sales teams atinfos@oncodna.com or +32 (0)71 18 35 00

CO N TACT US

OncoDNA S.A,Rue Louis Breguet 1,6041 Gosselies, Belgium +32 (0) 71 18 35 00 infos@oncodna.com www.oncodna.com

H OW TO S E LE C T TH E R I G HT S O LUTI O N

* Breast HR+ can be done upon request.

ctDNA DNA from PBMCs

ONCODEEP® ONCOSTRAT&GO® ONCOSTRAT&GO®

Stage I or II

Stage III

Stage IV for :

NSCLC, Colorectal, Breast (HR+ or HER2+), CUP

Stage IV for :

TNBC, Ovarian, Pancreas, Prostate *

Stage IV for:

Rest of the cancer types

: Recommended : Accepted : Strongly discouraged

IMPORTANT�FOR�CUP:�Always�clearly�state�“CUP”�when�ordering�your�analysis�(never�“unknown”�or�other�wording).�This�is�to�ensure�we�perform�the�most�suitable�analysis).