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. 2024 Nov 30;13(11):3083-3095.
doi: 10.21037/tlcr-24-525. Epub 2024 Nov 28.

Evaluation of the ASPYRE-Lung targeted variant panel: a rapid, low-input solution for non-small cell lung cancer biomarker testing and experience from three independent sites

Sarah E Herlihy  1 , Caren Gentile  1 , Samantha J Scott  2 , Brandon A Smith  2 , Kathryn A Stoll  2 , Kala F Schilter  2 , Justyna M Mordaka  3 , Rebecca N Palmer  3 , Christina Xyrafaki  3 , Elizabeth Gillon-Zhang  4 , Candace King  4 , Ryan T Evans  4 , Amanda S Green  4 , Ana-Luisa Silva  3 , Magdalena Stolarek-Januszkiewicz  3 , Kristine von Bargen  3 , Iyelola Turner  3 , Chau Ha Ho  3 , Alejandra Collazos  3 , Nicola D Potts  3 , Dilyara Nugent  3 , Jinsy Jose  3 , Eleanor R Gray  3 , Elyse Shapiro  4 , Wendy J Levin  4 , Aishling Cooke  3 , Barnaby W Balmforth  3 , Robert J Osborne  3 , Honey V Reddi  2   4 , Vivianna M Van Deerlin  1
Affiliations

Evaluation of the ASPYRE-Lung targeted variant panel: a rapid, low-input solution for non-small cell lung cancer biomarker testing and experience from three independent sites

Sarah E Herlihy et al. Transl Lung Cancer Res. .

Abstract

Background: Many patients with non-small cell lung cancer (NSCLC) lack access to highly effective approved targeted therapeutics due to multiple gaps in biomarker testing. Challenges in comprehensive molecular testing include complexities associated with the need to assess the presence of multiple variants, costs of running multiple sequential assays per sample, high assay quality control (QC) failure rates, clinical need for rapid turn-around time (TAT) to initiate therapy, and insufficient tissue samples. The ASPYRE-Lung NSCLC assay addresses gaps in multiplexed testing by simultaneously analyzing DNA and RNA, detecting 114 actionable genomic variants across 11 genes, consistent with current NSCLC treatment guidelines. This study was to assess the ease of adoption and performance of ASPYRE-Lung in third-party laboratories, comparing concordance across sites and with orthogonal methods.

Methods: ASPYRE-Lung was established at two academic centers with multiple operators per site. Assay concordance was evaluated across three sites using 77 patient samples [61 derived from formalin-fixed paraffin-embedded (FFPE) tissue and 16 from cytology specimens].

Results: Reproducibility for all 77 samples yielded a positive percent agreement (PPA) of 100% and negative percent agreement (NPA) of 99.99%. Concordance with next-generation sequencing (NGS)-based methods across all three sites was high with PPA of 97.2% and NPA of 99.96%.

Conclusions: ASPYRE-Lung assay is a cost-effective, easy to adopt testing method requiring no specialized expertise or complicated bioinformatics, with the potential to inform genomic data on small tissue samples, thus enabling all patients with NSCLC to undergo biomarker testing in a timely manner and benefit from appropriate targeted therapies.

Keywords: Non-small cell lung cancer (NSCLC); biomarker; molecular; targeted therapy.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-525/coif). All authors report that this work was supported by Biofidelity Ltd., UK. S.E.H. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. She served as technical consultant for potential investors at Biofidelity (Oct 2023 to Jan 2024). She received honoraria and travel expenses from ThermoFisher to present on NSCLC at a corporate workshop at AMP 2024. C.G. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. S.J.S. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. B.A.S. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. K.A.S. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. K.F.S. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. J.M.M. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. J.M.M. is an employee of Biofidelity Ltd. and has financial interest including salary, stocks, and stock options. R.N.P. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. R.N.P. is an employee of Biofidelity Ltd. and has financial interest including salary, stocks, and stock options. C.X. reports that Biofidelity provided all materials (reagents, consumables, travel expenses to laboratories) to complete the work. C.X. is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. E.G.Z. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. E.G.Z. is an employee of Biofidelity Inc. and has financial interest including salary, stock, and stock options. C.K. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. C.K. is an employee of Biofidelity Inc. and has financial interest including salary, stock, and stock options. R.T.E. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. R.T.E. is an employee of Biofidelity Inc. and has financial interest including salary, stock and stock options. A.S.G. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. A.S.G. is an employee of Biofidelity Inc. and has financial interest including salary, stock, and stock options. A.L.S. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. A.L.S. is an employee of Biofidelity Inc. or Biofidelity Ltd. and has financial interest including salary, intellectual property, stock, and stock options. M.S.J. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. M.S.J. is an employee of Biofidelity Ltd. and has financial interest including salary, intellectual property, stock, and stock options. K.v.B. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. K.v.B. is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. I.T. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. I.T. is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. C.H.H. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. C.H.H. is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. A. Collazos reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. A. Collazos is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. N.D.P. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. N.D.P. is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. D.N. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. D.N. is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. J.J. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. J.J. is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. E.R.G. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. E.R.G. is an employee of Biofidelity Ltd. and has financial interest including salary, stock, and stock options. E.S. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. E.S. is an employee of Biofidelity Inc. and has financial interest including salary, stock, and stock options. E.S. is a former employee of Adaptive Biotechnologies, which have no interests in the work presented herein. W.J.L. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. WJL. is a consultant of Biofidelity Inc. and has financial interest including consultancy fees and work-related travel to AACR 2024 where data from this work was presented. A. Cooke reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. A. Cooke was an employee of Biofidelity Ltd. and has financial interest including salary and stock. B.W.B. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. B.W.B. reports that Biofidelity Ltd. has provided travel expenses for work-related travel to AACR 2024 where data from this work was presented. B.W.B. is an employee of Biofidelity Ltd. and has financial interest including salary, intellectual property, stock, and stock options. R.J.O. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. R.J.O. was an employee of Biofidelity Ltd., and has financial interest including salary, stock, and stock options. H.V.R. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. H.V.R. was a consultant of Biofidelity Inc. and had financial interest including consultancy fees. H.V.R. is a current employee of Belay Diagnostics, which have no interests in the work presented herein. V.M.V.D. reports that Biofidelity provided all materials (reagents, consumables, etc.) to complete the work. The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
Schematic of ASPYRE-Lung workflow, instrument and time requirements. Analysis of the real-time PCR data takes place using a cloud-based turnkey analysis platform, and results show detection of specific variants (e.g., EGFR exon 19 deletion), with no need for further bioinformatic interpretation. PCR, polymerase chain reaction.
Figure 2
Figure 2
Samples analyzed in this study, source and orthogonal characterization method. A breakdown of sample type and the orthogonal test result is in Tables S1,S2. FFPE, formalin-fixed paraffin-embedded; TNA, total nucleic acid; FNA, fine needle aspirate.
See this image and copyright information in PMC

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