Genomic Drivers of Response to Immunotherapy

Unmet Need
Tumor mutational burden (TMB) is a measurement of mutations carried by tumor cells and is but one emerging biomarker for some types of cancer, including non-small cell lung cancer.  Currently, there is a lack of standardization for tumor mutational burden calculation and reporting. Different tests may report different measurements, and since there is currently no one way of calculating TMB it is difficult to use as a biomarker.  To achieve consistency and accurate reporting across tests, it is imperative to create some sort of standardization to arrive at clinically meaningful results, which will support informed decision-making for patients.
 
Technology Overview
Researchers at Johns Hopkins University have recently developed a new diagnostic algorithm which integrates several molecular markers to more accurately calculate response to immune checkpoint blockade therapies.  Investigators developed a new method to estimate ‘corrected tumor mutation burden’ (cTMB) adjusted for tumor purity within specimen samples that more accurately predicts treatment outcome.  Unlike current companion diagnostics for immune checkpoint therapies that measure one or two tumor indications, this new diagnostic algorithm can identify individuals that will respond or progress on immunotherapy using a model that incorporates corrected tumor mutation burden, smoking-related mutation signatures, receptor tyrosine kinase (RTK) activating mutations, and HLA genetic variation.  This new approach is an improvement in personal genome diagnostics which aims to complement current cancer immune checkpoint blockade therapies.
 
Stage of Development
Clinical data available

Publications
Anagnostou et al. Dynamics of Tumor and Immune Responses during Immune Checkpoint Blockade in Non-Small Cell Lung Cancer.  Cancer Res. 2019 Mar 15;79(6):1214-1225.
 

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