Predicting immunotherapy response

OncoDNA's most comprehensive solutions to better guide immunotherapy options for cancer patients

What is immunotherapy ?

Today’s most promising cancer therapy is immunotherapy. These  treatments stimulate the patient’s immune system to destroy his/her cancer cells. Some drugs recognize specific molecules on the surface of cancer cells while others can bind to immune cells to help them kill cancer cells.

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Approved treatments and markers

For the moment, there are 5 treatments approved for different cancers: 2 PD-1 inhibitors (Nivolumab / Opdivo® and Pembrolizumab / Keytruda®) and 3 PD-L1 inhibitors (Atezolizumab / Tecentriq®, Durvalumab / Imfinzi® and Avelumab /

Bavencio®).
There are currently only two companion diagnostics that have been associated with some drugs: firstly the expression of PD-L1 associated only with Keytruda® in NSCLC and bladder cancer and secondly MSI testing associated with all anti PD-1 (Keytruda® and Opdivo®) in solid tumors.

Identification criteria for good responders

Standalone markers have shown some promising results. However it has been reported that one biomarker might not be sufficient to get the best possible predictive value. Given the complexity of tumor-immune system interactions, predicting response to immunotherapy will most probably require intricate test strategies to accurately identify patients with the best chance of responding. Additional biomarkers (Tumor Mutational Burden, presence of infiltrating CD8+ cells,…) are still under investigation but their significance is heavily supported by scientific evidence and literature.

Our strategy

Since 2014 we have been using PD-L1 and CD8 expression levels to predict potential benefits of immunotherapies. Taking into account the latest publications and official guidelines, we have improved the test further to offer the most comprehensive approach on the market to solid tumor profiling.

Immunotherapy response is now assessed using these 3 additional criteria:

MSI (microsatellite instability) evaluation by fragment analysis of specific microsatellites.

– Analysis of several genes associated with sensitivity or resistance to immunotherapy (as recently published or presented during ASCO 2017). These include APLNR, JAK2, JAK1, POLE and STK11, as well as the 4 genes responsible for DNA Mismatch Repair (MRR) (MLH1, MSH2, MSH6 and PMS2).

– To assess tumor mutational burden (TMB), we have not only increased the size of the regions we cover by NGS, but also enriched the panel with specific regions associated with high TMB, and developed a new algorithm that takes into account the median number of mutations per cancer type.

Personalized immunogram

The purpose of analyzing these 5 biomarkers is to have a complete immune profile of the tumor. The results of all the test are integrated into a pentagon radar chart, called an immunogram, which clearly displays the probability of response to immunotherapy.

This innovative feature is now implemented in all our OncoDEEP and OncoSTRAT&GO solutions.

Reporting in OncoSHARE has been also updated to display these improved features in our solutions. We created a new widget for immunotherapy response assessment, where the personalized immunogram of each patient can be easily assessed.

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OncoDEEP improvements

At OncoDNA, we are keeping our promise to continuously improve our solutions. OncoDEEP, our first solution, is now in its 4th version and, while it is still the most cost-effective solution to evaluate the best options for chemotherapy and hormonal- and targeted therapies, we have recently increased its power of prediction of immunotherapy response with our newest development, adding several genes associated with sensitivity or resistance to immunotherapy and also MSI and TMB analyses to the PD-L1 and CD8+ expression levels which we already tested.

We have also improved our OncoDEEP panel by adding 139 SNPs to measure the loss of heterozygosity (LOH) or hemizygosity related to chromosome regions like 1p/19q or associated with genes such as RB1, TP53, PTEN, CDKN2A and CDKN2B.
We now also sequence the whole CDS of BRCA1 and BRCA2 associated with sensitivity to platinum and PARP inhibitors.

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OncoSTRAT&GO improvements

OncoSTRAT&GO combines the analysis of a solid biopsy sample (from the primary tumor or a metastasis) and the analysis of a liquid biopsy (from a blood sample). This integrated approach, which combines DNA and protein profiling of the cancer tissue sample with heterogeneity detection in the circulating tumor DNA (ctDNA), provides a complete molecular and genetic profile of the tumor. This comprehensive analysis facilitates the prediction of response to new and promising immunotherapies and targeted therapies as well as to classic chemotherapies.

The new version of OncoSTRAT&GO was also improved by adding MSI and TMB to the solid biopsy testing part of this already very comprehensive solution, so as to enhance immunotherapy response prediction. We also increased the number of genes we cover by NGS in the liquid biopsy sample to a total of 40.

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