MH Guide - Wegweiser für die genombasierte Therapieplanung (Broschüre für Onkologen)

Wegweiser für die genombasierte Therapieplanung MH Guide interpretiert komplexe molekulare Analysen und unterstützt Sie bei der evidenzbasierten Therapieempfehlung für Ihre Krebspatienten

MH Guide – Information für Onkologen

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Das könnte Sie interessieren:

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Die Vorteile von MH Guide

Ihre Therapieentscheidung, unterstützt durch weltweit verfügbare klinische Evidenz

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Die sieben Schritte für eine MH Guide Analyse

Der MH Guide Report

So erreichen Sie Molecular Health

MH Guide für die Falldiskussion im molekularen Tumorboard

Sie haben Fragen? Kontaktieren Sie uns unter +49 6221 43851-150 oder Kundendienst@molecularhealth.com

MH_Brosc

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hoose the best treatment for your patients.

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1 Die Vorteile von MH Guide

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Molekulare Daten für die Präzisionsmedizin übersetzen MH Guide ist eine Analysesoftware, die Molekularpathologen und Onkologen bei der Interpretation umfangreicher molekularer Datensätze unterstützt. MH Guide kann unabhängig von der verwendeten Sequenziertechnologie komplexe NGS-Datensätze

lesbar machen und automatisiert genetische Varianten identifizieren, die für die Behandlung von Krebspatienten von Bedeutung sind. Diese Informationen werden in klinisches Wissen übersetzt, das Sie bei der individuellen Therapieentscheidung unterstützt.

So profitieren behandelnde Ärzte von MH Guide: • Umfassende Informationen zu relevanten Biomarkern des Tumors und deren klinischer Bedeutung • Information zu Behandlungsmöglichkeiten, insbesondere für Krebspatienten mit fortgeschrittener Erkrankung, mit seltenen Erkrankungen oder für jene, bei denen die Möglichkeiten der Standardtherapie ausgeschöpft sind

• Hinweise auf relevante klinische Studien für Ihre Patienten • Informationen zu möglichen Nebenwirkungen, Wechselwirkungen oder Wirkstoffresistenzen • Eine digitale Plattform zur interdisziplinären Fallbesprechung in molekularen Tumorboards

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2 Ihre Therapieentscheidung, unterstützt durch weltweit verfügbare klinische Evidenz Der MH Guide Prozess Diagnostische und molekularpathologische Labore setzen unsere softwarebasierte Invitro-Diagnostik-Anwendung MH Guide ein, um relevante Biomarker in Tumorproben zu identifizieren und behandelnden Ärzten Informationen über individuelle Therapie- und Studienoptionen zur Verfügung zu stellen. Die Software vergleicht dazu die Daten der Patientenprobe mit aktuellem publiziertem biomedizinischem Wissen und Arzneimittelinformationen. Dabei liefert MH

Guide relevante Informationen zu identifizierten, relevanten Biomarkern und deren klinischer Bedeutung in den jeweiligen Krebsentitäten. Diese Informationen werden in einem übersichtlichen Patientenreport zusammengefasst. Für Sie heißt das, wichtige Informationen über wirksame und sichere medikamentöse Therapieoptionen sowie verfügbare klinische Studien werden Ihnen zur Verfügung gestellt – ganz im Sinne der Präzisionsmedizin.

Sie haben Fragen? Kontaktieren Sie uns unter +49 6221 43851-150 oder Kundendienst@molecularhealth.com

Integration von MH Guide in die klinische Routine

2.

Beauftragung der Molekulardiagnostik

Molekularpathologie 3.

NGS-Analytik

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Upload der Daten im MH Order Portal

Onkologie/Tumorboard Indikationsstellung

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Ortsunabhängige Fallbesprechung im MTB und Therapieentscheidung

Why deep understanding of the cancer’s molecular profile is key for treatment success in oncology

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Making therapeutic options visible: the MH Guide Report

Klinische Varianteninterpretation

Each tumor is unique, with individual patterns of DNA mutations, gene recombination, and gene fusions, amplifications, deletions, and insertions. The changes can alter protein function and protein expression, which may constitute targets for personalized cancer therapies.

Which gene variants are clinically significant? How severe is the tumor mutational burden?

Which therapy is best suited for an individual cancer patient? And which patients are more likely to experience adverse events?

In order to answer these questions, it is crucial to analyze each cancer sample as intensively as possible, and use the best molecular and clinical data, and drug and disease information available worldwide.

MH Guide uses expertly reviewed and up-to-date biological, clinical, and drug related information. This wealth of data makes MH Guide the best choice to help you analyze the molecular profile of tumor samples and support you as you choose the best treatment for your patients.

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Sample report: Lung adenocarcinoma* *(2 of 11 pages)

Patient ID — — Case ID Date of birth —

Sex Ethnicity Country Trial ZIP code

NGS data

Clinical variant interpretation (CVI): Identification and interpretation of relevant gene variants

Identified biomarkers

Identified therapeutic options and clinical studies

Get most out of your patient’s genomic data Advances in sequencing technologies enable scientists and physicians to generate massive quantities of data using next-generation sequencing (NGS). However, identifying and interpreting the relevant gene variants and their meaning for treatment choice is still challenging.

The CE IVD certified MH Guide analyzes NGS data of your patient to gain deep insight into the molecular profile of the patient’s tumor. MH Guide can analyze NGS data from whole exome sequencing data with the complete set of over 20,000 functional genes, or customized gene panels.

The MH Guide report delivers all information about identified, clinically relevant gene variants in a comprehensive format to choose the best treatment for your patients.

MH Guide allows you to have full control over your patient data, and your report while ensuring highest patient data security.

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Molekularpathologischer Befund mit MH Guide Report MH_Broschüre_Onkologie_ELCC.indd 4-6

Male — US —

Collected Tumor cellularity Barcode Sample type

— — — —

Labtest

—

Software version

—

Tissue type Metastatic

Patient ID — — Case ID Date of birth —

Lung adenocarcinoma Diagnosis — ICD-10-CM code — MeSH ID/term Additional MeSH IDs —

Primary tumor site — Surgical pathology — — — General dataset ID — CVI dataset ID — Organizational unit —

Ordering — physician — Facility Email — Phone — Fax — Product MH Guide — Report

ABCB1 not identified

ALK 1 fusion, 1 SNV

BRAF not identified

ROS1 1 del

Potential impact Effective

STK11 not identified

TP53 not identified

EGFR not identified

ERBB2 not identified

KRAS not identified

MET not identified

NF1 not identified

NRAS not identified

PIK3CA not identified

Treatment

Disease

Disease details

Guideline

Evidence Level

Brigatinib

Non-Small Cell Lung Cancer

Squamous cell carcinoma, Adenocarcinoma (with mixed subtypes), Large cell carcinoma

NCCN

1 for first-line therapy as a single agent if ALK rearrangement discovered prior to first-line systemic therapy

RET not identified

Recommended use: Single-agent therapy for ALK rearrangement-positive recurrent, advanced or metastatic disease Overview of prognostic and diagnostic findings

Overview of potential treatment impacts

Potential impact

2 Ineffective

1 Safety

Treatment

Effective

Lorlatinib

Effective

Ceritinib

Effective

Brigatinib

0 Prognostic

Drug approval*

Biomarker

0 Diagnostic

VAF

Biomarker score

Clinical trials found 8

Trials

ALK/EML4 (fusion)

—

2

ALK/EML4 (fusion)

—

3

Approved

ALK/EML4 (fusion)

—

5

Dabrafenib

Approved

G6PD p.R285H (SNV)

99.56%

—

Ineffective

Crizotinib

Approved

ALK p.L1196M (SNV)

23.80%

—

Ineffective

Alectinib

Approved

ALK p.L1196M (SNV)

23.80%

—

Signed by 11 Dec 2019 12:20 (UTC+01:00)

Molecular Health GmbH, Kurfuersten-Anlage 21, 69115 Heidelberg | www.molecularhealth.com | +49 6221 43851-150

• as first-line therapy • for patients who are intolerant to crizotinib • as subsequent therapy following disease progression on first-line therapy with crizotinib, except in cases of symptomatic systemic disease with an isolated lesion • as continuation of therapy if used first line, except in cases of symptomatic systemic disease with multiple lesions

Trials

Approved

Approved

Safety

Effective

Ceritinib

Non-Small Cell Lung Cancer

Squamous cell carcinoma, Adenocarcinoma (with mixed subtypes), Large cell carcinoma

NCCN

1 for first-line therapy as a single agent if ALK rearrangement discovered prior to first-line systemic therapy 2A for all others 2B for locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease

Recommended use: Single-agent therapy for ALK rearrangement-positive recurrent, advanced or metastatic disease

* in the patient's disease; VAF = Variant allele frequency Biomarker score: AMP score and CVI score. Clinically approved: Approved biomarker (by the FDA, EMA, or NCCN) to predict a specific effect in the patient's disease. Clinical: Not yet approved biomarker for the patient's disease. Observed in clinical studies as a potential biomarker to predict a specific effect of the drug. Preclinical: This biomarker has not yet been observed/tested in patients to predict a specific effect of the drug. It is supported by preclinical evidence or translational data.

You can find more details on the biomarker score (AMP and CVI score) in the glossary.

Order date 14 Nov 2019 Report Version 5

2A for all others 2B for locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease

SUMMARY

3 Effective

Lung adenocarcinoma Diagnosis — ICD-10-CM code — MeSH ID/term Additional MeSH IDs —

MEDICAL GUIDELINES Relevant treatment information from medical guidelines and potential impact based on detected biomarkers

Mutational status of commonly mutated genes in the patient disease

MH Guide Report A

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Phone —

• as first-line therapy • for patients who are intolerant to crizotinib • as subsequent therapy following disease progression on first-line therapy with crizotinib except in cases of symptomatic systemic disease with an isolated lesion • as continuation of therapy if used first line, except in cases of symptomatic systemic disease with multiple lesions

Effective

Order date 14 Nov 2019 Report Version 5 Page 1 of 11

Lorlatinib

Non-Small Cell Lung Cancer

Squamous cell carcinoma, Adenocarcinoma (with mixed subtypes), Large cell carcinoma

Signed by 11 Dec 2019 12:20 (UTC+01:00)

NCCN

2A for all others 2B for locoregional recurrence or symptomatic local disease (excluding mediastinal lymph node recurrence with prior radiation therapy) with no evidence of

Phone —

Molecular Health GmbH, Kurfuersten-Anlage 21, 69115 Heidelberg | www.molecularhealth.com | +49 6221 43851-150

Page 2 of 11

The report lists identified, clinically relevant gene variants of the patient’s tumor, targetable biomarkers and their clinical validity.

One of the key benefits of the report is the list of therapeutic options with country-specific drug approval status, along with the potential impact of each drug for individual patients.

The MH Guide report can be adapted to your individual needs.

Our scientific field support teams are available whenever you need them.

13.02.20 16:38

3 MH Guide für die Falldiskussion im molekularen Tumorboard

Flexible Zusammenarbeit für eine schnelle Therapieentscheidung MH Guide kann molekulare Tumorboards (MTB) mit seiner flexiblen und interoperablen Benutzeroberfläche ideal bei den Fallbesprechungen unterstützen. Verschiedene Experten können mit den Analyseergebnissen arbeiten. Sie können zusätzliche Informationen zum Zustand des Patienten oder zu bisherigen Therapien ergänzen sowie Ergebnisse gezielt für die Besprechung in der Konferenz filtern.

MH Guide liefert damit nicht nur evidenzbasierte Biomarker- und Therapieinformationen, sondern kann die Zusammenarbeit im MTB optimieren und Zeit einsparen.

Sie haben Fragen? Kontaktieren Sie uns unter +49 6221 43851-150 oder Kundendienst@molecularhealth.com

Vorteile für Tumorboards durch MH Guide: • Kosteneffiziente, hochpräzise Berichte für Ihr Tumorboard

• Erhebliche Zeitersparnis für die an der Therapieentscheidung beteiligten Ärzte

• Offenes System zur Einbindung in Ihre digitale Infrastruktur (z. B. Verknüpfung mit EMR-Datenbanken)

• Direkte, zeitunabhängige Zusammenarbeit mit dem molekularpathologischen Labor

• Ortsunabhängiger Cloud-Zugriff für alle beteiligten Experten

• Die Möglichkeit, Tumorboards zu standardisieren und Diagnoseabläufe zu vereinfachen

4 Die sieben Schritte für eine MH Guide Analyse 1

Indikationsstellung Der Onkologe stellt die Indikation für die molekularpathologische Diagnostik.

Molekulardiagnostik beauftragen

2 3 4 5

Der Onkologe sendet Probenmaterial (Tumorbiopsie oder Tumorprobe) mit Überweisung (Muster 10) und Arztbrief an seinen Pathologen vor Ort. Er beauftragt dabei den Nachweis tumorrelevanter Mutationen.

NGS-Analyse durchführen Der Pathologe führt neben weiteren Untersuchungen des Tumors (a) die NGS-Analyse selbst durch oder (b) beauftragt dazu ein molekularpathologisches Labor.

NGS-Daten in MH Guide hochladen Das ausführende Labor führt die NGS-Analyse durch und lädt die Daten im Web-Portal zur MH Guide Auswertung hoch.

NGS-Daten analysieren MH Guide analysiert die NGS-Daten, vergleicht sie mit bereitgestellten Informationen der Dataome-Wissensdatenbank und ermöglicht die Erstellung eines individuellen Berichts.

Befunderstellung

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Der ausführende Pathologe bearbeitet den MH Guide Bericht und zeichnet ihn frei. Das ausführende Labor oder der Pathologe vor Ort fasst die gesamten pathologischen Ergebnisse und Informationen aus dem MH Guide Bericht zusammen.

Auswahl von Therapieoptionen Der Onkologe erhält den Befund von seinem zuständigen Pathologen einschließlich individueller Therapieinformationen und möglicher Studien.

Sie haben Fragen? Kontaktieren Sie uns unter +49 6221 43851-150 oder Kundendienst@molecularhealth.com

5 Der MH Guide Report

Evidenzbasierte Entscheidungshilfe für die Behandlungsplanung Der MH Guide Report gibt einen Überblick über die klinisch relevanten Biomarker sowie die daraus abgeleiteten Therapieoptionen. Er beinhaltet die Variantenbezeichnung sowie die Bewertung und klinische Validität der Biomarker nach internationalen Richtlinien (AMP, ASCO, CAP).

Für die Therapieplanung liefert der MH Guide Report einen Überblick über: • Potenzielle Behandlungsmöglichkeiten • Unwirksame Arzneimittel sowie solche mit Sicherheitsbedenken • Informationen zu relevanten rekrutierenden klinischen Studien Der Report kann durch Integration von Analyseergebnissen aus Nicht-NGS-Methoden wie FISH, Immunhistochemie (IHC) oder qPCR ergänzt werden. So bieten sich Ihnen alle relevanten Ergebnisse auf einen Blick.

the theMH MH Guide Guide ReaR Sample Sample report: report: Lung Lung ade

Sample Sample report: report: Lung Lung ade a Sample Sample report: report: Lung Lung adea *(2 of*(2 11 of pages) 11 pages) *(2 of*(2 11 of pages) 11 pages)

*(2 of*(2 11 of pages) 11 pages) Alles im Blick:

Informationen zum vorliegenden Tumor

Identified Identified therapeutic therapeutic options options and and clinical clinical Identified Identified therapeutic therapeutic Identified Identified therapeutic therapeutic studies studies options options and and clinical clinical options options and and clinical clinical studies studies studies studies

— ID — Patient IDPatient —ID — Case ID Case Date of birth Date—of birth —

— ID — Patient IDPatient —ID — Case ID Case — — Patient IDDate Patient ID — Date of birth —of birth Primary tumor site — Primary tumor site — Sex Male Sex Collect —ID Collected — Case ID Case Darstellung derMale detektierten — Surgical pathology — Ethnicity Ethnicity — — Surgical pathology Tumor Tumor Date of birth Date —of birth — cellularity Biomarker deren klinischer — Country US undUS Country Tissue type Barcode Barcod Tissue type— — ZIP — MetastaticMetastatic — — Trial ZIP Sex Trial Sample type Sample Validität Primary tumor Primary sitetumor — site — Sex Male Male Collected Collect code code Surgical pathology Surgical pathology — — Ethnicity Ethnicity — — General dataset Tumor Tumor — ID — Labtestcellularity GeneralIDdataset Labtes Primary tumor Primary site tumor — — Sex Sex Male Male Collected Collect Country Country US US Tissue type Tissue type Barcode Barcod CVI dataset IDdataset —ID site — CVI — pathology Surgical — — ——ZIP ——Surgical — Ethnicity Ethnicity Tumor cellularity Tumor Software version Softwa Trial ZIP Trial Metastatic Metastatic Sample type Sample Organizational unitpathology — unit — Organizational — — code code Country Country US US Tissue type Tissue type— Barcode Barcod General dataset GeneralIDdataset — ID — Labtest Labtes — ZIP — Metastatic — Trial ZIP Trial Metastatic— Sample type Sampl CVI dataset CVIIDdataset—ID — code code Zulassungsstatus der Medikamente Software Softwa dataset General IDdataset ID in —the Labtest Labtes MutationalMutational status of commonly mutated genes in patient disease statusGeneral of commonly mutated genes patient diseaseversion Organizational Organizational unit —the unit — in Bezug auf die Indikation CVI dataset CVIIDdataset—ID — ABCB1 ABCB1 ALK EGFR ERBB2 ERBB2 KRAS MET ALKBRAF BRAF EGFR KRAS Software version Softwa unit — not unit des not Patienten not 1 Organizational not— not 1 fusion, 11 Organizational fusion, not not not not not not

identified SNVof commonly identified identified identified identified iden identified SNVof identified identified identified Mutational Mutational status status commonly mutated genes mutated in the genes patient in the disease patient diseaseidentifi

ABCB1 ABCB1 ALK BRAF BRAF EGFR EGFR ERBB2 ERBB2 KRAS KRAS MET STK11 ALK TP53 STK11 TP53 Mutational status of commonly status of mutated mutated in the genes patient disease patient ROS1 Mutational ROS1 Zusammenfassung: Dieses Feld not not 1not fusion, 11not fusion, 1 notgenes notcommonly not not notin the not notdiseasenot not 1identified del 1identified del SNV SNV identified identified identified identified identified identified identifi iden ABCB1 vom ABCB1 ALK ALKBRAF BRAF EGFR EGFR ERBB2 ERBB2 KRAS KRAS MET identified identified kann Anwender frei identified not not1 fusion, 11 fusion, not 1 notnot notnot notnot notnot genutzt werden STK11 STK11 TP53 TP53 identified identified SNV SNVidentified identified identified identified identified identified identified identifi iden ROS1 ROS1 not not not not 1 del 1 del SUMMARY SUMMARY identified identified identified identified STK11 STK11 TP53 TP53 ROS1 ROS1 not notnot not 1 del 1 del identified identified identified identified Overview O o Overview Overview of potential of treatment potential treatment impacts impacts

SUMMARY SUMMARY 3 Effective 3 Effective 2 Ineffective 2 Ineffective 1 Safety1

Safety

0 Progn

SUMMARY SUMMARY Overview Overview of potential of treatment potential treatment impacts impacts

Overview O o Potential impact Potential impact Treatment Treatment Drug Drug approval*Biomarker Bio 3 Effective 3 Effective 2 Ineffective 2 Ineffective 1 Safety 1 approval* Safety 0 Progn Overview oO Overview of Overview potential oftreatment potential treatment impacts impacts ALK/EML4 ALK 3 Effective Effective 3Effective Effective 2 Ineffective 2 Ineffective 1 Safety 1 Safety 0 Progn Lorlatinib Lorlatinib Approved Approved (fusion) (fus Potential impact Potential impact TreatmentTreatment Drug approval* Drug approval*BiomarkerBio

ALK/EML4ALK Effectiveimpact Effectiveimpact Treatment Ceritinib Ceritinib Approved Approved Potential Potential Treatment Drug approval* Drug approval*ALK/EML4 BiomarkerALK Bio (fusion) (fus (fusion) (fus ALK/EML4AL ALK/EML4ALK (fusion) (fu ALK/EML4ALK (fusion) (fus (fusion) (fus ALK/EML4AL Effective Effective Ceritinib CeritinibApproved Approved G6PD p.R285 G6 (fusion) (fu ALK/EML4ALK Safety Safety Dabrafenib Dabrafenib ApprovedApproved Effective Effective BrigatinibBrigatinib ApprovedApproved (SNV) (SN Effektiv (fusion) (fus ALK/EML4AL Effective Effective Brigatinib Brigatinib Approved Approved ALK p.L1196M ALK (fusion) (fu G6PD p.R285 G6 IneffectiveIneffective Crizotinib Crizotinib ApprovedApproved Ineffektiv Safety Safety Dabrafenib Dabrafenib ApprovedApproved (SNV) (SN (SNV) (SN G6PD p.R285 G6 Safety Safety DabrafenibDabrafenib Approved Approved Mögliches Sicherheitsrisiko ALK p.L1196M ALK (SNV) (SN ALK p.L1196M ALK IneffectiveIneffective Alectinib AlectinibApprovedApproved IneffectiveIneffective Crizotinib Crizotinib ApprovedApproved (SNV) (SN (SNV) (SN ALK p.L1196M AL * in the patient's * in thedisease; patient'sVAF disease; = Variant VAFallele = Variant frequency allele frequency IneffectiveIneffective Crizotinib Crizotinib Approved Approved (SNV) (SN Biomarker Biomarker score: AMP score: scoreAMP andscore CVI score. and CVI Clinically score. Clinically approved: approved: Approved Approve biomar ALK p.L1196M ALK Ineffective Ineffective Alectinib Alectinib Approved Approved disease.

Clinical: disease.

Not Clinical: yet approved Not yet approved biomarker biomarker for the patient's for thedisease. patient'sObserved disease. Ob in c (SNV) (SN drug. Preclinical: drug. Preclinical: This biomarker This biomarker has not yethas been notobserved/tested yet been observed/tested in patients intopatie pre ALK p.L1196M AL Ineffective Approved Approved * in Ineffective the patient's * in data. the disease; patient's VAF disease; =Alectinib Variant VAFallele =Alectinib Variant frequency allele frequency translational translational data.

(SNV) (SN Biomarker Biomarker score: AMP score: score AMP and score CVI and CVI Clinically score.

Clinically approved: approved: Approved Approve biomar You can find You more can find details more ondetails the biomarker on score. the biomarker score (AMP score and (AMP CVI score) and CVI in the score) glossary. in the Clinical: disease.

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You can find Youmore can find details more on details the biomarker on the biomarker score (AMPscore and CVI (AMP score) and CVI in the score) glossary. in the Lorlatinib Lorlatinib ApprovedApproved Effective Effective Zusammenfassung und Klassifikation Lorlatinib Lorlatinib Approved Approved Effective Effectiveder identifizierten Effective Effective BrigatinibBrigatinib ApprovedApproved Effective Effective Ceritinib CeritinibApprovedApproved Therapieoptionen

ans to to generate generate .owever, However, identifying identifying ans to to generate generate ans to generate to generate tment choice choice is still is still .eatment owever, However, identifying identifying .owever, However, identifying identifying tment eatment choice choice is still is still tment eatment choice choice is still is still gain n deep deep insight insight egain yze NGS data data from from nNGS deep deep insight insight gain n deep deep insight insight nctional functional genes, genes, eyze NGS NGS data data from from

Order date 14 Nov Order 2019 date 14 Nov 2019 Report VersionReport 5 Version 5

Signed by Signed by 11 Dec 2019 12:20 11 Dec (UTC+01:00) 2019 12:20 (UTC+01:00)

Molecular Health Molecular GmbH, Health Kurfuersten-Anlage GmbH, Kurfuersten-Anlage 21, 69115 Heidelberg 21, 69115| Heidelberg www.molecularhealth.com | www.molecularhealth.com | +49 6221 4 Order date 14 Nov Order 2019 date 14 Nov 2019 Report VersionReport 5 Version 5

Signed by Signed by 11 Dec 2019 12:20 11 Dec (UTC+01:00) 2019 12:20 (UTC+01:00)

Molecular Health Molecular GmbH, Health Kurfuersten-Anlage GmbH, Kurfuersten-Anlage 21, 69115 Heidelberg 21, 69115Signed | Heidelberg www.molecularhealth.com | www.molecularhealth.com | +49 6221 4 Order date 14 Nov Order 2019 date 14 Nov 2019 by Signed by Report Version 5Report Version 5

11 Dec 2019 12:20 11(UTC+01:00) Dec 2019 12:20 (UTC+01:00)

Molecular Health Molecular GmbH, Health Kurfuersten-Anlage GmbH, Kurfuersten-Anlage 21, 69115 Heidelberg 21, 69115| www.molecularhealth.com Heidelberg | www.molecularhealth.com | +49 6221 4

Sie haben Fragen? Kontaktieren Sie uns unter +49 6221 43851-150 oder Kundendienst@molecularhealth.com

Sample report: Lung adenocarcinoma* *(2 of 11 pages) *(2 of 11 pages)

Patient ID — — Case ID Date of birth —

Lung adenocarcinoma Diagnosis — ICD-10-CM code — MeSH ID/term Additional MeSH IDs Lung — adenocarcinoma Diagnosis Patient ID — — — ICD-10-CM code Case ID — MeSH Date of birth — — ID/term Primary tumor site — Ordering — Sex Male Collected Additional MeSH IDs — physician Surgical pathology — Ethnicity — Tumor cellularity — — — — Facility Country US Tissue type Barcode — — Email — Trial ZIP — Metastatic Sample type — Primary tumor site — Ordering — Sex Male Collected Phone — code physician Surgical pathology General dataset ID — — Labtestcellularity — Ethnicity — Tumor Fax — — — — Facility CVI dataset — Country US Tissue type ID Barcode Product MH Guide — — — Software version Email — Organizational unit — Trial ZIP Metastatic Sample type — Report Phone — code — General dataset ID — Labtest Fax — CVI dataset ID — Product MH Guide Mutational status of commonly mutated genes Organizational unit in —the patient diseaseSoftware version — — Report ABCB1 ALK BRAF EGFR ERBB2 KRAS MET NF1 NRAS PIK3CA RET not 1 fusion, 1 not not not not not not not not not identified status SNVof commonly identified identified identified Mutational mutated genes in the patient diseaseidentified identified identified identified identified identified ABCB1 ROS1 not 1 del identified

ALK STK11 1not fusion, 1 SNV identified

BRAF TP53 not identified

STK11 ROS1 not 1 del SUMMARY identified

TP53 not identified

EGFR not identified

ERBB2 not identified

KRAS not identified

2 Ineffective

NF1 not identified

NRAS not identified

PIK3CA not identified

Relevant

MEDIC

Potenti

Relevant Effect

Potenti

Effect

RET not identified

Recomm Single-a Overview of prognostic and diagnostic findings

Overview of potential treatment impacts

SUMMARY 3 Effective

MET not identified

MEDIC

1 Safety

0 Prognostic

Overview of potential treatment impacts Potential impact 2 Ineffective Treatment 1 Safety Drug approval* 3 Effective

0 Diagnostic

Overview of prognostic and diagnostic findings Biomarker Biomarker score 0 PrognosticVAF 0 Diagnostic

Clinical trials found 8

Trials

Recomm Single-a

Clinical trials found Trials 8 Trials

Lorlatinib Treatment

Approved Drug approval*

ALK/EML4 (fusion) Biomarker

— VAF

Effective Effective

Ceritinib Lorlatinib

Approved Approved

ALK/EML4 ALK/EML4 (fusion) (fusion)

— —

3 2

Effective Effective

Brigatinib Ceritinib

Approved Approved

ALK/EML4 ALK/EML4 (fusion) (fusion)

— —

5 3

Safety Effective

Dabrafenib Brigatinib

Approved Approved

G6PD p.R285H ALK/EML4 (SNV) (fusion)

99.56% —

— 5

Ineffective Safety

Crizotinib Dabrafenib

Approved Approved

ALK p.L1196M G6PD p.R285H (SNV) (SNV)

23.80% 99.56%

— —

Recomm Single-a

Ineffective Ineffective

Alectinib Crizotinib

Approved Approved

ALK p.L1196M ALK p.L1196M (SNV) (SNV)

23.80% 23.80%

— —

Recomm Single-a

Effective Potential impact

Biomarker score

2 Trials

Effect

* in the patient's disease; VAF = Variant allele frequency Biomarker score: AMP score and CVI score. Clinically approved: Approved biomarker (by the FDA, EMA, or NCCN) to predict a specific effect in the patient's ALK p.L1196M Ineffective Alectinib Approved 23.80% — of the disease.

Clinical: Not yet approved biomarker for the patient's disease. Observed in clinical studies as a potential biomarker to predict a specific effect (SNV) drug. Preclinical: This biomarker has not yet been observed/tested in patients to predict a specific effect of the drug. It is supported by preclinical evidence or * in the patient's disease; VAF = Variant allele frequency translational data.

Biomarker AMP score and CVI score.score Clinically approved: Approved biomarker (by the FDA, EMA, or NCCN) to predict a specific effect in the patient's You can findscore: more details on the biomarker (AMP and CVI score) in the glossary. disease. Clinical: Not yet approved biomarker for the patient's disease. Observed in clinical studies as a potential biomarker to predict a specific effect of the drug. Preclinical: This biomarker has not yet been observed/tested in patients to predict a specific effect of the drug. It is supported by preclinical evidence or translational data.

You can find more details on the biomarker score (AMP and CVI score) in the glossary.

Order date 14 Nov 2019 Report Version 5

Signed by 11 Dec 2019 12:20 (UTC+01:00)

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Molecular Health GmbH, Kurfuersten-Anlage 21, 69115 Heidelberg | www.molecularhealth.com | +49 6221 43851-150 Order date 14 Nov 2019 Report Version 5

Signed by 11 Dec 2019 12:20 (UTC+01:00)

Molecular Health GmbH, Kurfuersten-Anlage 21, 69115 Heidelberg | www.molecularhealth.com | +49 6221 43851-150

Effect

Effect

Effect

Order date 14 Report Versio Page 1 of 11

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Molecular

Order date 14 Report Versio Page 1 of 11

Molecular

The report lists identified, clinically relevant gene va

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