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Antimicrobial Resistance (AMR)

Test Information

Xpert® Insight Breast Cancer[1] is a new test in development at Cepheid. This prototype multiplex, mRNA expression test is designed to measure the expression of six genes (3 biomarkers and 3 controls) in formalin-fixed, paraffin-embedded breast cancer tissue from patients with early stage breast cancer. The weighted expression of these genes will be combined with two clinical factors (tumor size and nodal status) using a proprietary algorithm to produce a binary risk score (high risk vs low risk) that is designed to predict the likelihood of distant disease recurrence in the next 10 years. 

This test which was originally developed by Oncomark, an Ireland-based biotechnology company, and was initially named OncoMasTR™.  Cepheid and OncoMark started collaborating in 2018 to explore development of a version of the OncoMasTR assay for use on the GeneXpert® system. This collaboration was successful, ultimately leading to the acquisition of OncoMark and the OncoMasTR technology by Cepheid in March 2021. Cepheid intends to market the test under the name Xpert Insight Breast Cancer.

The development of the OncoMasTR test began in 2014. Below, please find highlights of the major development milestones over the last seven years.     

[1] Product in development. Not for use in diagnostic procedures. Not reviewed by any regulatory body.

Year

 

Development Milestone(s)

 

2014

Original invention relating to the OncoMasTR technology was jointly filed by the University College of Dublin and Trinity College Dublin with inventors  Bracken, Lanigan and Gallagher.

 

2015

Relevant peer reviewed publication: 
Lanigan et al. FEBS J 2015; 282:3455-73. Delineating transcriptional networks of prognostic gene signatures refines treatment recommendations for lymph node-negative breast cancer patients.

Key points from the Lanigan et al. discovery study:

  • ARACNe: Bioinformatic method that constructs gene regulation networks.
  • “What genes regulate the prognostic genes in three existing prognostic signatures for breast cancer?” 
  • A panel of ten ‘Master Transcriptional Regulators’ (MTRs) was identified.
  • A basic risk score was constructed from a subset of the MTRs shown to be prognostic for breast cancer survival (mRNA and protein level).

 

2016

Development of OncoMasTR at OncoMark

Key conclusions from the product development work:

  • Using a clinical specimen cohort with long term outcomes (‘Consecutive Cohort’, n=225, 37 distant recurrence events), a 3-gene signature, including the FOXM1, PTTG1, and ZN367 genes (FPZ, hereafter), was development and optimized.    
  • From this 3-gene signature, three FPZ-based risk scores were derived:

              i.    A molecular only numeric risk score (0-100)
             ii.    A molecular and clinical numeric risk score (0-10)
            iii.    A molecular and clinical categorical risk score (low if risk <5, high if risk ≥5)

 

2017

Relevant peer reviewed publication: 
Moran et al. Cancer Res. 2017; 77(9):2186-90. Master Transcriptional Regulators in Cancer: Discovery via Reverse Engineering Approaches and Subsequent Validation. Conceptual bioinformatic framework for finding master control genes.

Training and verification of OncoMasTR assay was completed, with poster presentation of the data at the San Antonio Breast Cancer Symposium. 

In parallel, further development and validation studies were conducted according to CLSI guidelines (Analytical Validation of OncoMasTR according to CLSI Guidelines: Precision, Linearity, Sensitivity, RNA Input, Interference, Kit stability, manuscript under review).

 

2018

CE mark was obtained for the OncoMasTR assay.  

Three, independent, external clinical validation studies were initiated, using pre-specified risk scores for the OncoMasTR assay:  

  1. TransATAC (n=646)
  2. TAILORx (n=404), Irish subset of broader TAILORx trial.
  3. ABCSG-8 (n=1,087)

Together, these studies included over 2,000 ER+, HER2-, early-stage (LN0-3) breast cancer patients.

Key conclusions from the clinical validation studies:

  • OncoMasTR was significantly prognostic for distant recurrence (DR) in all three studies.  
  • In two of the studies (TransATAC and the TAILORx subset) where data was available to support comparative analyses, OncoMasTR provided superior prognostic value to Oncotype Dx Recurrence Score (RS).

Cepheid and OncoMark begin collaboration discussions to develop a GeneXpert version of the OncoMasTR assay.

 

2019

OncoMark initiates real-world, decentralized evaluations of the OncoMasTR assay was initiated at three sites:  

  1. St James’ Hospital, Ireland
  2. Beaumont Hospital, Ireland
  3. Utrecht Medical Centre, The Netherlands

Key conclusions from the beta-site testing and analytical validation (Analytical Validation of OncoMasTR according to CLSI Guidelines): 

  • OncoMasTR displays robust analytical performance and is potentially suitable for decentralized use. 
  • Overall precision of OncoMasTR was high, with a standard deviation of 0.16 (<2% of the 10-unit risk score range)
  • OncoMasTR scores were consistent across a >100-fold RNA input range
    • Across 4 testing sites, the continuous OncoMasTR risk score correlation coefficients were 0.94 – 0.96 and the categorical score concordance was 86 – 96%.

Cepheid and OncoMark enter into a formal collaboration to develop a GeneXpert version of the OncoMasTR assay. 

 

2020

Relevant peer reviewed publication: 
Buus R et al.  Clin Can Res. 2020; 26:623-31. Validation of the OncoMasTR risk score in estrogen receptor-positive/HER2-negative patients:  A TransATAC study.

Relevant peer reviewed publication:
Mazo et al. Cancers 2020; 12(5):1133. Multi-gene prognostic signatures and prediction of pathological complete response to neoadjuvant chemotherapy in ER-positive, HER2-negative breast cancer patients.

Cepheid assigns Xpert Insight Breast Cancer tradename to GeneXpert version of OncoMasTR assay.    

Cepheid demonstrates analytical equivalency of Xpert Insight Breast Cancer assay to OncoMasTR assay.    

Cepheid demonstrates the fidelity of risk score reporting between Xpert Insight Breast Cancer and OncoMasTR in characterized specimens.

 

2021

Relevant peer reviewed publication:  
Lynch, SM et al.  Eu J Can. 2021; 152:  78-79. Prognostic value of the 6-gene OncoMasTR assay in hormone receptor-positive HER2-negative early-stage breast cancer:  Comparative analysis with standard clinicopathological factors.  

Relevant peer reviewed publication: 
Filipits M et al.  Clin. Can. Res. 2021; (e-pub ahead of print) doi: 10.1158/1078-0432.CCR-21-1023. The OncoMasTR assay predicts distant recurrence in estrogen receptor-positive, HER2-negative early stage breast cancer:  A validation study in ABCSG Trial 8.

Cepheid acquires OncoMark and the OncoMasTR assay.  

Cepheid demonstrates clinical equivalency of Xpert Insight Breast Cancer to OncoMasTR in FFPE specimens with long-term outcomes.  

Cepheid initiates real-world evidence and clinical validation studies for the Xpert Insight Breast Cancer prototype test.

If you are interested in learning more, or engaging with Cepheid in a collaborative evaluation of the Xpert Insight Breast Cancer prototype test, please contact the Cepheid Medical and Scientific Affairs and Strategy team for Oncology at: MedSci.Oncology@Cepheid.com

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