The most comprehensive tumour investigation

exacta® is a comprehensive analysis of tumours. exacta® allows a therapy recommendation to be made for most cancer patients, based on clinical evidence and experience. Especially for rare solid tumours where no guidelines are available, in the advanced situation or for tumours that are difficult to treat, exacta® is providing an advantage. exacta® analyses millions of data points at the molecular level to identify all relevant targets for an individual therapy.

About exacta®

However, conventional ‘Standard of Care’ approach does not take into consideration the overall genetic architecture of a particular patient‘s tumour and consequently, patients could suffer due to failed therapies or aggressive relapse. It is, thus, imperative that the genetic architecture of the tumour is studied comprehensively before deciding the treatment plan, which has to be personalised to individual patients and their disease.

exacta® is a comprehensive in depth tumour gene expression analysis. It analyses 100’s of millions of data points at the molecular level to reveal all possible targets for precision drugs.

exacta® helps unravel the driver mutations and pathways that are propelling a particular person’s cancer through multi-analyte and multi-coordinate analysis over 20.805 genes in the cancer genome. This analysis helps identify drugs that would be most effective for a particular solid tumour. exacta®, thus enables a highly sophisticated treatment strategy beyond conventional perspective, even for difficult to treat or late stage cancers.

exacta® is particularly recommended for cancer patients where ...

<p>... first-line therapy has failed</p>

... first-line therapy has failed

<p>... cancer has relapsed</p>

... cancer has relapsed

<p>... cancer is high-grade / metastatic</p>

... cancer is high-grade / metastatic

<p>... newly diagnosed patients with difficult cancers such as stomach, oesophagus, pancreas, gall bladder, GIST etc.</p>

... newly diagnosed patients with difficult cancers such as stomach, oesophagus, pancreas, gall bladder, GIST etc.

<p>... risk of therapy failure is high</p>

... risk of therapy failure is high

Methodology

  • Targeted Genes
    SNVs, CNVs, Amplifications, Mutation load, Germline mutations

  • RNA Sequencing
    KEGG pathways (Disease, Actionable, Resistance)

  • Pharmacogenetics
    Genotyping for CYP450, drug transporters for drug toxicity and efficacy

  • Chemosensitivity
    In vitro cell based assay for testing drugs identified, including other recommended combinations

  • Liquid Biopsy
    Mutation load, Tumour heterogeneity

Advantages

Most Optimal Targeted Therapy Selection:
exacta® identifies possible molecular targets and cell cycle pathways to find the most appropriate molecular targets for targeted therapy. All relevant biomarkers for targeted therapy selection, including mutations, deletions, gene rearrangement, gene amplification / expression, are analysed. Confounding impact of simultaneous resistant molecular alterations on sensitizing mutations giving better therapy selection than single gene test based therapy.

Most Optimal Cytotoxic Therapy Selection:
Cytotoxic drug response / resistance of cancer genome, based on DNA and gene expression. Comprehensive exacta® includes chemosensitivity testing for cytotoxic drug efficacy prediction.

Drug Repurposing:
With recurrent or high grade cancer which has progressed despite therapy. exacta® can explore all possible therapeutic options by analysing all molecular alterations.

Longitudinal Disease / Therapy Monitoring:
Comprehensive exacta® enables effective tumour burden monitoring, therapy response monitoring and helps detect early therapy failure or recurrence.

Therapy Recommendation (TR):
Proprietary exacta® analysis provides best therapy combination option to treating physician.

Comprehensive

Parameters and Methods of Analysis
  • Tumour DNA analysis
    452 genes ( tissue biopsy ) / 411 genes ( liquid biopsy )
  • Mutations and Gene Amplifications
  • Fusion / Rearrangements
    51 genes (tissue biopsy) / 12 genes (liquid biopsy)

  • Tumour Gene Expression
    20.805 genes

  • Cellular pathways as per KEGG
  • Chemosensitivity *
    up to 100 drugs

  • Liquid Biopsy Cell free DNA (cfDNA)
  • ICC Immunocytochemistry (mTOR, VEGFR, EGFR, etc.)
  • Microsatellite Instability (MSI / MMR)
    (tissue biopsy / liquid biopsy)

  • Tumour Mutation Burden (TMB)
  • Relevant IHC PD-L1, AR etc.
    (tissue biopsy)

  • Circulating Tumor Cells (CTCs)
  • Platforms
    NGS, Microscopy, Arrays, ddPCR, CE

  • Therapy Recommendations (TR)
  • Pharmacogenetic Guidance
  • Immunotherapy Guidance
  • Sanger Sequencing to rule out germline nature of high MAF alterations
  • Sensitive ddPCR assays to detect therapy relevant low MAF alterations
  • Longitudinal Monitoring for MAF Comparisons of Repeat Tests
  • Limit of Detection (MAF)
    2.5 % (Tissue), 0.1 % (cfTNA)

  • Sensitivity at 0.1 % MAF (cfTNA)
    97.06 %

  • Sensitivity at 2.5 % MAF
    96.43 %

  • Positive Predictive Value
    100 %

* Subject to availability of adequate sample.

100s of Millions of Data Points Analyzed

(from Peripheral Blood and / or Fresh Tissue and / or FFPE Block / or Liquor)

Cell Free DNA

Exosomal 20.805 mRNAs

Driver Mutations; Rearrangements; Insertions and Deletions from 452 / 411 genes

Direct Live Tumour Cell Assessment

Tumor Cell Cycle Pathways

+

Artificial Intelligence / Database based, multi-level iterative algorithm to determine optimum (most favorable + least toxic) drugs and drug combinations

=

Therapy Recommendations

Sample requirement

,

30 ml blood in DCGL tube and EDTA tube both

Optional: 20 ml blood in DCGL tube and EDTA tube both as well as fresh tissue sample in DCGL transport media (4-6cm3 or 5 cores); alternative: FFPE tissue block

Precautions:

Please wait 24 hours after chemotherapy/PET-CT/MRI, before sampling blood

Please wait 10 days after blood transfusion.

Turn Around Time (TAT):

10 - 14 days from receipt of the sample

Contact

Dr. Stefan Schuster,<p>Managing Director Europe</p>

Dr. Stefan Schuster

Managing Director Europe

FAQ

What is Therapy Recommendation (TR)?

TR is a document that lists the various drugs (single drugs or drugs in combination) found to be beneficial for the patient based on detailed analysis of multiple biomarkers which is carried out during exacta® analysis. TR is given as part of the exacta® report. Based on the established efficacy and safety profile, these drugs are assigned a preference list. Where drug combinations may work better than single drugs, these will be indicated.

If two patients have the same histopathological cancer type, and one of them under-goes exacta® analysis, can the other patient receive the same treatment as indicated in the TR of the first patient?

Just as each patient is unique, so is each cancer. No two patients’ cancers are alike. Even two similar patients (e.g. age, gender, height, lifestyle) with the same type of cancer (e.g. lung) will have different molecular profile of tumours. Hence each patient should perform an individual exacta® test.

How is the TR used?

Therapy, based on the recommendations in TR, must be selected by the treating oncologist after suitability of the treatment has been determined as well as health and fitness of the patient have been evaluated. The selected treatment must be administered only under the supervision of the treating oncologist. The TR is only a recommendation of drugs that have high potential for success and benefit to the patient.

Why is it important to start treatment immediately?

Cancer can be very aggressive and may evolve rapidly; the tumour profile can change dramatically over time. Starting the treatment immediately is essential as it is the best strategy to counter the aggressiveness of the cancer. If there is a long enough delay the cancer may gain resistance to treatments and re-analysis may be required.

What kind of drugs will be recommended / given to the patient?

Only drugs that have been approved by the FDA will be recommended and be administered. These will include drugs that are FDA approved for use in same cancer / other cancer / other non-cancerous diseases. The TR will not recommend any investigational antineoplastic drugs / FDA-unapproved drugs.

Are there any follow-up molecular tests to assess the result of recommended therapy?

Liquid biopsy can be extremely beneficial for real-time patient monitoring because it allows modification of therapy as well as recurrence monitoring when the patient is in remission. So, precision oncology molecular tests (cancertrack™) will not only provide information for selection of therapy, but will also allow the oncologist to monitor the therapy in real time and make decisions that will benefit quality of life, overall survival, progression free survival.