1253P - Analytic validation and implementation of OncoDEEP: A pan-cancer comprehensive genomic profiling NGS assay for assessing homologous recombination deficiency (HRD)

Background

Comprehensive genomic profiling (CGP) and reliable molecular characterization of solid tumors using NGS technology has become a key tool to facilitate biomarker-matched therapy selection. With a broad spectrum of therapies already approved or in clinical trials, rapid and scalable detection of an evolving number of therapeutically relevant genomic alterations and complex biomarkers is required. The all-in-one OncoDEEP® solution integrates both, an up-to-date comprehensive NGS panel >1MB powered by Twist Bioscience hybrid capture technology in combination with OncoDNA’s bioinformatic data analysis and clinical interpretation software suite (OncoKDM and MERCURY) resulting in an integrated theranostic report. The CE-IVD approved assay covers single-nucleotide variants (SNVs), copy number variants (CNVs), deletions and insertions (indels) and loss of heterozygosity (LOH) in 638 genes and facilitates the assessment of key complex biomarkers / signatures such as homologous recombination deficiency (HRD), tumor mutational burden (TMB), or microsatellite instability (MSI). In addition, fusion gene detection (ALK, RET, ROS1) and MET exon 14 skipping events are detectable on DNA level.

Methods

Extensive validation of OncoDNA’s OncoDEEP® workflow was performed on DNA from >300 FFPE tissue specimens in combination with commercial reference standards (e.g. HRD, fusion reference material) to assess analytical accuracy, sensitivity, and precision.

Results

In this initial validation study, the OncoDEEP® kit exhibited high analytic concordance, sensitivity and specificity consistent with requirements allowing the implementation of this CE-IVD assay for routine clinical application. We successfully participated in external quality assessment programs for e.g. HRD testing.

Conclusions

Our results demonstrate that OncoDNA’s OncoDEEP® kit provides an efficient pan-cancer solution for accurate comprehensive genomic profiling for biomarker-matched therapy selection, including HRD, TMB and MSI. The integrated software suite allows for clinical interpretation and reporting with robust analytical performance.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

OncoDNA.

Disclosure

M. Trautmann: Financial Interests, Invited Speaker: OncoDNA; Financial Interests, Advisory Board: Roche, Novartis, Bristol Myers Squibb. All other authors have declared no conflicts of interest.