MH Guide - Pathfinder for genome-based therapy planning (Information for oncologists)

Pathfinder for genome-based therapy planning MH Guide interprets complex molecular analyses and helps you recommend evidence-based treatments for your cancer patients

MH Guide – Information for oncologists

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This might interest you:

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The benefits of MH Guide

Your treatment decision, supported by worldwide clinical evidence

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An MH Guide analysis in seven steps

The MH Guide report

How to reach Molecular Health

Questions? Please contact us on +49 6221 43851-150 or via CustomerService@molecularhealth.com

3 MH Guide for case discussions in molecular tumor boards

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hoose the best treatment for your patients.

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1 The benefits of MH Guide

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NICAL DATA CLI

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LECULAR DATA

Translate molecular data into precision medicine MH Guide is an analysis software that supports molecular pathologists and oncologists in the interpretation of large molecular datasets. Independent of the sequencing technology used, MH Guide can make complex NGS datasets readable,

and automatically identify genetic variants that are relevant for treating cancer patients.

This information is translated into clinical knowledge that helps you make individual therapy decisions.

How attending physicians benefit from MH Guide: • Comprehensive information on relevant biomarkers and their clinical significance

• Information on relevant clinical trials for your patients

• Information on treatment options, especially for cancer patients with advanced disease, with rare diseases, or for those who have exhausted the options of standard therapy

• Information on possible side effects, drug-drug interactions, or drug resistance • A digital platform for interdisciplinary case discussion in molecular tumor boards

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2 Your treatment decision, supported by worldwide clinical evidence The MH Guide process Diagnostic and molecular pathology laboratories use our software-based in-vitro diagnostic application MH Guide to identify relevant biomarkers in tumor samples, and to provide attending physicians with information on individual treatment and trial options. The software compares the patient sample data with current, published biomedical knowledge and drug data.

MH Guide provides pertinent information about identified, relevant biomarkers and their clinical significance in the respective cancer entities. All of this information is summarized in a clear patient report. This way, you receive key information on effective and safe drug treatment options and available clinical trials – entirely in line with precision medicine.

Questions? Please contact us on +49 6221 43851-150 or via CustomerService@molecularhealth.com

Integrating MH Guide in your clinical routine

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Order molecular diagnostics

Molecular pathology 3.

NGS analytics

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Upload data via MH Order Portal

Oncology/tumor board Indication

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Remote case discussion in the MTB and treatment decision

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

Clinical variant interpretation

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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Molecular pathology findings with the 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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• 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

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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.

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3 MH Guide for case discussions in molecular tumor boards

Flexible collaboration for a rapid treatment decision With its flexible and interoperable user interface, MH Guide can optimally support molecular tumor boards in case discussions.

Authorized experts can work with the analysis results, add information about the patient’s condition or previous therapies, and filter results specifically for discussion in the conference.

MH Guide thus not only provides evidencebased biomarker and therapy information, but can also optimize collaboration within the MTB, and save time.

Questions? Please contact us on +49 6221 43851-150 or via CustomerService@molecularhealth.com

How tumor boards benefit from MH Guide: • Cost-efficient, highly accurate reports for your tumor board

• Significant time savings for physicians involved in therapy decisions

• Easy integration in your digital infrastructure (e. g. linking with EMR databases)

• Direct collaboration with the molecular pathology laboratory at any time

• Remote cloud access for all experts involved

• The ability to standardize tumor boards and simplify diagnostic workflows

4 An MH Guide analysis in seven steps 1 2 3 4 5 6 7

Indication The oncologist establishes the indication for molecular pathology diagnostics.

Order molecular diagnostics The oncologist sends sample material (tumor biopsy or tumor sample) with referral and physician’s letter to their local pathologist, ordering the detection of tumor-relevant mutations.

Perform NGS analysis In addition to examining the tumor, the pathologist (a) performs the NGS analysis or (b) commissions a molecular pathology laboratory to do so.

Upload NGS data to MH Guide The laboratory performs the NGS analysis and uploads the data to the web portal for MH Guide evaluation.

Analyze NGS data MH Guide analyzes the NGS data, compares it with information provided by the Dataome knowledge base, and lets users generate a customized report.

Findings The performing pathologist edits the MH Guide report and signs it.

The performing laboratory or on-site pathologist summarizes all of the pathology results and the information from the MH Guide report.

Select therapy options The oncologist receives the findings from the pathologist in charge, including individual therapy options and possible clinical trials.

Questions? Please contact us on +49 6221 43851-150 or via CustomerService@molecularhealth.com

5 The MH Guide report

Evidence-based decision aid for treatment planning The MH Guide report gives an overview of the clinically-relevant biomarkers as well as the therapeutic options derived from them. It includes the variant name as well as biomarker assessment and clinical validity according to international guidelines (AMP, ASCO, CAP).

For treatment planning, the MH Guide report provides an overview of: • Potential treatment options • Ineffective drugs and those with safety concerns • Information on relevant, recruiting clinical trials The report can be supplemented by integrating analysis results from non-NGS methods such as FISH, immunohistochemistry (IHC), or qPCR. This gives you a clear overview of the relevant results.

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) Everything at a glance:

— ID Patient IDPatient Information on the present tumor

— —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 — Male Collect —ID Collected — Case ID Case — Surgical pathology — — Surgical pathology Tumor Tumor Date of birth Date —of birth — cellularity — US Tissue type Barcode Barcod Tissue type— — MetastaticMetastatic — — Sample type Sample Primary tumor Primary sitetumor — site — Male Collected Collect

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

Sex Male Sex Ethnicity Ethnicity — Country Country US — ZIP Trial ZIP Sex Trial Sex Male code code pathology Surgical pathology — Ethnicity Ethnicity — — Surgical Tumor Tumor General dataset — ID — Labtestcellularity GeneralIDdataset — Labtes Primary tumor Primary site tumor — — Sex Sex Male Male Collected Collect Country Country US of the US Tissue type Tissue type Barcode Barcod CVI dataset IDdataset —ID site — CVI — Depiction detected pathology Surgical — — ——ZIP ——Surgical — Ethnicity Ethnicity Tumor Tumor Software version Softwa Trial ZIP Trial Metastatic Metastatic Samplecellularity type Sample Organizational unitpathology — unit — Organizational — biomarkers and their clinical validity — 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 codestatus of the drugs with Approval 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 — respect to the patient’s indication CVI dataset CVIIDdataset—ID — ABCB1 ABCB1 ALK EGFR ERBB2 ERBB2 KRAS MET ALKBRAF BRAF EGFR KRAS Software version Softwa unit — not unit not 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 Summary: This can not not 1not fusion, 1field 1not fusion, 1 be notcommonly notgenes not not notin the not notdiseasenot not 1identified del 1identified del SNV identified identified identified identified identified identified identifi iden ABCB1 ABCB1 ALK ALK BRAF BRAF EGFR EGFR ERBB2 ERBB2 KRAS KRAS MET identified identified utilized freely bySNV the useridentified not not1 fusion, 11 fusion, not 1 notnot notnot notnot notnot 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 Effective Effective BrigatinibBrigatinib ApprovedApproved Effective Effective Ceritinib CeritinibApprovedApproved (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 Effective (fusion) (fus ALK/EML4AL Effective Effective Brigatinib Brigatinib Approved Approved ALK p.L1196M ALK (fusion) (fu G6PD p.R285 G6 IneffectiveIneffective Crizotinib Crizotinib ApprovedApproved Ineffective Safety Safety Dabrafenib Dabrafenib ApprovedApproved (SNV) (SN (SNV) (SN G6PD p.R285 G6 Safety Safety Approved Approved Possible safety risk DabrafenibDabrafenib 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.

Not Clinical: yet VAF approved Not yet VAF approved biomarker biomarker forallele the patient's for thedisease. patient'sObserved disease. Ob in c *disease. in the patient's * in thedisease; patient's disease; = Variant allele = Variant frequency frequency drug. Preclinical: drug.

Preclinical: This biomarker This has yethas been not observed/tested yet Clinically been observed/tested in patients intopatie pre Biomarker Biomarker score: AMP score: score AMP andbiomarker score CVI not score. and CVI Clinically score. approved: approved: Approved Approve biomar translational translational data.Not data. disease.

Clinical: disease.

Clinical: yet approved Notof yet approved biomarkerbiomarker for the patient's for thedisease. patient'sObserved disease. Ob in c Electronic signature You find You more can find details ondetails the biomarker onnot the yet biomarker score (AMP score and (AMP CVI score) andinCVI inpatients the score) glossary. inpatie the drug.can Preclinical: drug.

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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 Effective Effective Summary and classification of ApprovedApproved the identified options Lorlatinib Lorlatinib Approved Approved Effective Effectivetherapy

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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

Questions? Please contact us on +49 6221 43851-150 or via CustomerService@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)

Phone —

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

Phone —

Molecular

Order date 14 Report Versio Page 1 of 11

Molecular

The report lists identified, clinically relevant gene va

6 How to reach Molecular Health

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