Discover the future of automated variant annotation MH Guide interprets complex genetic data quickly and accurately – for the growing challenges of today and tomorrow
MH Guide – Information for pathologists
This might interest you:
1
2
3
The benefits of MH Guide
Use global knowledge locally – evidencebased treatment planning
Big Data analytics for laboratories
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Clinical variant interpretation
MH Guide analysis in seven steps
The MH Guide report
7 How to reach Molecular Health
Questions? Please contact us on +49 6221 43851-150 or via CustomerService@molecularhealth.com
1 The benefits of MH Guide NICAL DATA CLI
MO
LECULAR DATA
Automated variant interpretation – fast, precise, efficient MH Guide is an in-vitro diagnostic software approved in Europe. It assists molecular pathologists working with large molecular datasets. Independent of the sequencing technology used, MH Guide can interpret complex datasets and automatically identify
genetic variants that are relevant for the treatment of cancer patients. This information is translated into clinical knowledge that supports you in making individual therapy decisions.
How laboratories benefit from MH Guide • Automated interpretation of NGS data for small and large panels, as well as wholeexome sequencing (WES) and data from other compatible analytical methods • Access to comprehensive, up-to-date variant interpretations through Dataome, one of the world’s largest databases for biomedical information.
• Rapid, quality-assured clinical variant annotation and report generation • Highly customizable results report: users can filter for relevant information and integrate their own data and sources • Digital platform for interdisciplinary case discussion in molecular tumor boards
2 Use global knowledge locally – evidence-based treatment Integrating MH Guide in your clinical routine
2.
Order molecular diagnostics
Molecular pathology 3.
NGS analytics
4.
Upload data via MH Order Portal
Oncology/tumor board Indication
8.
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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6.
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. M
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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.
7.
Primary tumor site — Surgical pathology — — Tissue type — Metastatic
Male — US —
Patient ID — — Case ID Date of birth —
Lung adenocarcinoma Diagnosis — ICD-10-CM code — MeSH ID/term Additional MeSH IDs —
Collected Tumor cellularity Barcode Sample type
General dataset ID — CVI dataset ID — Organizational unit —
Ordering — physician — Facility Email — Phone — Fax — Product MH Guide — Report
— — — — —
Labtest Software version
—
Molecular pathology findings with the MH Guide report MH_Broschüre_Onkologie_ELCC.indd 4-6
Questions? Please contact us on +49 6221 43851-150 or via CustomerService@molecularhealth.com
ABCB1 not identified
ALK 1 fusion, 1 SNV
BRAF not identified
ROS1 1 del
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
Potential impact Effective
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 3 Effective
2 Ineffective
1 Safety
Treatment
Effective
Lorlatinib
Effective
Ceritinib
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
Approved
G6PD p.R285H (SNV)
99.56%
—
Crizotinib
Approved
ALK p.L1196M (SNV)
23.80%
—
Ineffective
Alectinib
Approved
ALK p.L1196M (SNV)
23.80%
—
Brigatinib
Safety
Effective
Signed by 11 Dec 2019 12:20 (UTC+01:00)
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.
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
Dabrafenib
Ineffective
Effective
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
Potential impact
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
1.
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
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 information. 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. You can customize this report and integrate it in your pathology report, for tumor board discussions. This way, clinical colleagues quickly receive conclusive findings: all of the key information on effective and safe drug treatment options and available clinical trials – entirely in line with precision medicine.
3 Big Data analytics for labs Automated variant interpretation with data from Dataome – the “learning database” The Dataome knowledge base is the foundation for the MH Guide analysis platform. Developed over a decade, Dataome is a proprietary global data platform for biomedical knowledge that combines three innovations: Dataome Capture: The platform uses artificial intelligence and machine learning to mine molecular and clinical data sources in real time. For clinical variant interpretation, data is curated by experts (molecular biologists, molecular pathologists, oncologists).
Dataome Knowledge: Dataome screens and bundles the world’s medical literature. This allows analysis data to be placed in a medical context. Dataome Analytics: Complex genetic tumor data, such as NGS data, is efficiently and automatically matched by MH Guide with information obtained from Dataome and used for clinical variant interpretation.
4 Clinical variant interpretation
Translate precise variant interpretation into treatment options MH Guide combines the variants, pre-classified according to ACMG standards, with therapy-relevant findings – and lists the relevant information: • Identified variant (germline or somatic, zygosity)
• Impact and approval status of potential treatment options
• Disease associated with the variant
• Suitable clinical trials, if available
• Validity of identified predictive, prognostic, and diagnostic biomarkers
• Summary (so-called narrative)
Flexibility and transparency of variant evaluation • The MH Guide analysis can be customized by setting filters or implementing rules. • MH Guide gives the user full access to the evidence base of clinical variant interpretation.
Questions? Please contact us on +49 6221 43851-150 or via CustomerService@molecularhealth.com
The components of clinical variant interpretation (CVI) with MH Guide
e f
a
g
b ga
gb
h c
d
a
Variants
b
• Gene symbol • Variant name (HGVS) • Somatic or germline • Zygosity
d
Literature
Biomarker score
ga
CVI score (evidence level: preclinical [1–3], clinical [4–6], clinically approved [7]) AMP/ASCO/CAP category (tier I–IV)
gb
c
• List of diseases for which the biomarker has been described
e
• L ist of publications and their PubMed IDs
g
Diseases
Biomarker type • Predictive (effective, ineffective, safety) • Diagnostic • Prognostic
h
Narrative • Summary of CVI
Treatment options • List of therapies • CVI score •A ssociation for Molecular Pathology (AMP) category
f
Match quality How well does the interpretation match the variant and patient disease?
5 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 pathologist 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
6 The MH Guide report
Evidence-based decision aid for treatment planning The interactive MH Guide report gives an overview of all the important information on the biomarkers detected in a tumor sample. 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, IHC, or qPCR, and can be individualized and integrated into the local infrastructure thanks to standard digital formats.
Output formats are PDF, JSON, and XML
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. Preclinical: Thismore biomarker This biomarker has has been not observed/tested yet been observed/tested into pre the pathologist in charge translational translational data. data. 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
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
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 Patient ID — Diagnosis — — ICD-10-CM code Case ID — MeSH ID/term Date of birth — — 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 Ethnicity — Tumor General dataset ID — — Labtestcellularity — Fax — — — — Facility Country US Tissue type ID Barcode CVI dataset — Product — MH Guide — — — Email Softwaretype version Trial ZIP Metastatic Sample Organizational unit — — 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 not identified 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% — 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 (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
7 How to reach Molecular Health
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