Verification of the analytical performance of a molecular diagnostic for response to anti-PD1 therapy on the nCounter Dx Analysis System

Autor: Mingdong Liu, Afshin Mashadi-Hossein, Irena Pekker, Simina Popa, James Storhoff, Naeem Dowidar, Brett Wallden, Sean Ferree, Patrick Danaher, Matthew J. Marton, Celine Ngouenet, Amy Sullivan
Rok vydání: 2017
Předmět:
Zdroj: Journal of Clinical Oncology. 35:8-8
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2017.35.7_suppl.8
Popis: 8 Background: Pembrolizumab is a humanized anti-PD1 antibody that is approved for use in advanced melanoma, recurrent or metastatic head and neck squamous cell carcinoma, and metastatic non-small-cell lung cancer. It has also shown clinical activity in a number of other tumor types in clinical trials, but there is need for a precise and accurate test that can identify patients most likely to benefit from therapy. We have previously described the development and analytical performance of a NanoString RNA expression clinical trial assay, referred to here as the Tumor Inflammation Signature (TIS) assay, which is being evaluated as a patient enrichment biomarker in multiple solid tumor types for treatment with pembrolizumab. Here we describe additional performance data and analytical verification of reproducibility from tissue and RNA input range in multiple tumor types. Methods: Linearity and specificity were assessed with single targets or pools of in vitro transcribed RNAs with sequences matching the 18 biomarker and 10 normalization gene probe targets. The verification of the previously reported analytical precision from RNA and reproducibility from tissue was performed using independent samples from 11 tumor types. The biological variability of the signature within a patient sample was evaluated by testing multiple core punches from formalin fixed paraffin embedded (FFPE) tissue blocks. Results: The TIS assay’s measurement of the 28 genes was linear across a wide dynamic range ( ≥ 4 logs) and was highly specific with < 1% cross reactivity between probes. The assay was verified across the specified RNA input range with > 90% concordance at the low end (50ng) of the RNA input range. The total standard deviation of the anti-PD1 Predictor Score from tissue was verified as < 5% of the signature score range and > 90% concordance in biomarker high/low categorization within the biological replicates. Conclusions: The analytical performance of the NanoString TIS assay was verified to be robust. The assay is well suited for decentralized clinical testing and is currently under investigation to identify responders to anti-PD1 therapy in multiple tumor types in several clinical studies.
Databáze: OpenAIRE
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