DEVELOPMENTAL THERAPEUTICS—MOLECULARLY TARGETED AGENTS AND TUMOR BIOLOGY
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`e15056
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`Publication Only
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`MATRIX plasma-in-plasma contrived samples assessment and detection of MRD using the
`Personalis NeXT Personal assay.
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`Paul Labrousse; AstraZeneca, Waltham, MA
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`Background: Detection of circulating tumor DNA (ctDNA) has been shown to correlate with clinical
`outcome of oncology patients. Molecular residual disease (MRD) profiling by ctDNA is being rapidly
`deployed. Current tumor-informed MRD tests assess a relatively small number of personalised variants,
`placing limits on their detection sensitivity and ultimately leading to false-negative results due to
`insufficient assay limit of detection (LOD). Here we report a performance evaluation of the Personalis
`NeXT Personal tumor-informed MRD assay, using a novel design for contrived samples that are highly
`commutable to clinical samples, enabling robust assessment of these emerging MRD assays. Methods:
`Our novel samples were built from commercially acquired matched tumor and plasma samples, across
`different indications. The cancer plasma was diluted into a background of healthy donor plasma to
`create the 72 plasma-in-plasma samples in each study (total of 144). Personalis performed WGS on the
`matched solid tumor and normal samples from each patient. ~1800 somatic variants were selected for
`each patient. A personalized panel was designed and used to enrich for the selected targets in the
`individual plasma samples. An aggregated positive variant score was evaluated to determine the
`presence of ctDNA in each plasma sample. Results: MATRIX 1 panels averaged 1863 variants (range:
`1818 to 1888) selected for MRD tracking. With 152 clinically relevant variants and additional assay
`components, an average of 2206 variants were assessed per patient. MATRIX 2 panels averaged 1836
`variants (range: 1819 to 1867) selected for MRD tracking. With 2130 clinically relevant variants they
`averaged 4094 variants assessed per patient. In the MATRIX 1 study, tumor signal was detected in all
`analyzed samples, including 9 samples at 0.002% tumor plasma dilution, with an assay sensitivity of
`100%. The MATRIX 2 study showed tumor signal detected in 14 of 16 samples at 0.001% tumor
`plasma dilution. The 2 false negatives were reported at the 0.001% tumor plasma dilution. Thus, the
`assay sensitivity was 87.5% at the lowest dilution (0.001%) and 96.8% overall. Conclusions: The
`MATRIX plasma-in-plasma approach is a robust option for assessing the sensitivity of MRD assays to
`low levels of ctDNA. This approach addresses all parts of an MRD assay for both the plasma and tumor/
`normal tissues, and is the closest thing to real clinical samples while allowing direct interrogation of
`sensitivity. Additionally, it allows assessment of any genomic or epigenomic biological feature. The
`Personalis NeXT Personal assay shows ultra-high sensitivity with reproducible data down to the 1-3
`PPM range, and expansion of the personalized panel fixed clinical content allows tracking of more driver
`and resistance mutations with no impact to the MRD sensitivity. Research Sponsor: AstraZeneca.
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`© 2023 by American Society of Clinical Oncology. Visit meetings.asco.org and search by abstract for disclosure information.
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`Personalis EX2156
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