Therapeutic management

OmniSeq INSIGHT is intended for use by qualified health care professionals in accordance with professional guidelines in oncology for management of patients with solid neoplasms, and is not conclusive or prescriptive for labeled use of any specific therapeutic product.

Other

Tests performed
Interpretation performed in-house
Report generated in-house
Specimen preparation performed both in-house and at an outside lab
Wet lab work performed in-house

Test performance comments
PD-L1 technical component is performed at an outside lab. Some slide cutting and staining occurs at an outside lab

Contact Laboratory for detailed Analytical validity documents. Precision: Repeatability and reproducibility of alterations associated with Tier I mutations and platform-wide alterations, including agreement for small variants, CNA, MSI, TMB, fusions and splice variants were evaluated. Repeatability (5 replicates intra-run under same conditions) and reproducibility of inter-run replicates (3-49 replicates under … Contact Laboratory for detailed Analytical validity documents. Precision: Repeatability and reproducibility of alterations associated with Tier I mutations and platform-wide alterations, including agreement for small variants, CNA, MSI, TMB, fusions and splice variants were evaluated. Repeatability (5 replicates intra-run under same conditions) and reproducibility of inter-run replicates (3-49 replicates under different conditions) were assessed and compared across two different sequencers, five different reagent lots (combinations of assay and sequencing reagents), across multiple days (n=13) by multiple operators (n=3) with rotating barcodes. 134 specimens representing 128 tumors and 6 QC controls were evaluated for precision separately for DNA (n=90) an R A =44). Precisions studies assessed assay variability from nucleic acid library preparation through analytical pipeline analysis. Substitutions APA: 94.03% ANA: 99.99% Insertions APA: 99.22% ANA: 100% Deletions APA: 99.22% ANA 99.99% Copy gain/loss APA: 97.69% ANA: 99.81% MSI APA: 100% ANA: 95.92% Fusions APA: 94.25% ANA: 99.98% Splice Variants APA: 96.71% ANA: 99.95% TMB# APA: 3.3-9.6% overall CV Analytical Sensitivity (LoD): The Limit of Detection (LoD) of alterations assessed by QI-genomic profiling was evaluated at the platform level and at select variant positions. The LoDs for small variants is based on VAF and for non­ small variant alterations based on tumor purity. All LoD studies were performed at the lower recommended DNA (40ng) and RNA (20ng) input for QI-genomic profiling using diluted and undiluted clinical FFPE tumor (n=78) and contrived samples (n=1) selected for each of the variant classes. For each sample, three - six levels of dilution (neat to 1:32) dependent on starting tumor purity, alteration frequency and sample availability were evaluated with and without replication. Dilutions were performed by mixing normal DNA or RNA from FFPE specimens with the clinical FFPE specimens. Select FFPE specimens were also used to evaluate the LoD of specific mutations with Tier I evidence of clinical significance. The established analytical sensitivity ranges were confirmed at >= 95% call hit rate with FFPE clinical cases on a per variant level for Tier I alterations, and using all somatic variants identified in FFPE clinical cases representing a range of VAFs for hotspot and non-hotspot positions for platform-wide assessment. The small variant comparison study evaluated a test set of 428 qualified specimens. A total of 1151 unique somatic small variant positions from 88 genes, including 83 unique ins ions and 139 unique deletions from 32 genes were included in the study. Positive percent agreement (PPA) and negative percent agreement (NPA) between the QI-genomic profiling and the vNGS :assay was calculated for all small variant alterations, as well as for alterations binned by type: substitutions, insertions and deletions. Additional analytical concordance for specific Tier I variants are also summarized. All small variants PPA: 99.2% NPA: 99.96% Copy number aberrations (CNA): From a clinical perspective, CNA evaluation by QI-genomic profiling reports amplification (copy gain) for oncogenes and deletion (copy loss) for tumor suppressor genes. The CNA comparison study evaluated a test set of 562 specimens for gain and 451 for loss between the QI-genomic profiling and vNGS. Though the QI-genomic profiling assay is designed to detect copy number fold change in 59 genes, the copy gain concordance studies were limited to 17 genes for which orthogonal data was available: AR, CCND1, CCNE1, CDK4, CDK6, EGFR, ERBB2, FGFR1, FGFR2, KIT, KRAS, MET, MDM2, MYC, MYCN, PDGFRA and PIK3CA. Copy loss studies were restricted to ATM, BRCA1, BRCA2, and PTEN. Both the concordance of QI-genomic profiling and vNGS fold change (FC) values, and PPA/NPA agreement of copy number calls at the QI-genomic profiling cutoffs were calculated. A total of 10,824 CNA calls, including 9,219 for gains and 1,605 for losses were included in the study (Table 7). High correlation (R2 >0.91 and R>0.96) of copy gain fold change values (range 2.2 - 117) between the two platforms was observed for the 17 genes studied. All copy gains: PPA 99.6% NPA: 98.9% Tumor mutational burden (TMB): The analysis for concordance of TMB-High detection by QI-genomic profiling at the 10 mut/Mb cut point was performed using a CLEP approved vNGS targeted panel and an NCI validated whole exome sequencing (vWES) assay as comparators. 429 qualified samples representing 34 tumor types were evaluated, with 29 for WES. TMB concordance results at the 10 mutations per megabase cut point between QI-genomic profiling and the comparator assays are summarized. TMB: PPA: 87% NPA: 88% Microsatellite instability (MSI): The qualitative output for MSI (MSI-High vs. MS-Stable) in the QI-genomic profiling and CLEP approved vNGS assay were evaluated for concordance. PPA and NPA of MSI status between the two assays was calculated for 368 qualified samples studied (Table 9), including a subset of CRC (10%) and uterine cancer (4%) specimens. TMB: PPA: 96% NPA: 99.7% Fusions and splice variants: Overall there were ten clinically relevant overlapping genes between QI-genomic profiling and vNGS assay for the detection of fusions and splice variants from RNA which included for comparison 437 qualified samples from 35 different tumors and reference cell lines. Concordance results between 01- genomic profiling and the comparator assay for fusion and splice variant calling are summarized. All fusions: PPA: 93.4% NPA: 99.97% View more

OmniSeq INSIGHT is not conclusive or prescriptive for use of any specific therapeutic product. OmniSeq INSIGHT has been validated using genomic DNA and RNA from formalin fixed paraffin-embedded tumor samples. OmniSeq INSIGHT is designed to report somatic variants and is not intended to report germline variants. Clinical validity performance of … OmniSeq INSIGHT is not conclusive or prescriptive for use of any specific therapeutic product. OmniSeq INSIGHT has been validated using genomic DNA and RNA from formalin fixed paraffin-embedded tumor samples. OmniSeq INSIGHT is designed to report somatic variants and is not intended to report germline variants. Clinical validity performance of this test for predicting treatment effect of any specific therapeutic product has not been established. The assay has been validated using samples with a minimum of 20% tumor purity in the tissue area to be extracted. For the detection of copy number alterations (CNA), tumor purity above 30% yields consistent detection of fold change (FC) ≥2.2 for gain, and tumor purity above 50% yields consistent detection of FC ≤0.7 for loss. Concordance with other validated methods for the detection of copy number alterations (CNA), fusions and splice variants has been demonstrated for copy gain genes CCND1, CCNE1, CDK4, CDK6, EGFR, ERBB2, FGFR1, FGFR2, KIT, KRAS, MET, MDM2, MYC, and PIK3CA, copy loss genes ATM, BRCA1, BRCA2, and PTEN, fusion genes ALK, FGFR3, NTRK1, NTRK3, RET, and ROS1, and splice variant genes EGFR and MET. If clinically indicated, copy alterations and fusions identified in other genes tested by OmniSeq INSIGHT should be confirmed by additional testing. The MSI-High/MS-Stable designation by the OmniSeq INSIGHT test is based on genome-wide analysis of 130 potential microsatellite loci. The threshold for MSI-High/MS-Stable was determined by analytical concordance to a validated comparator NGS assay using colorectal, uterine and other cancer FFPE tissues. Samples with ≥20% MSI unstable sites are consider MSI-High, while samples with <20% unstable sites are considered MS-Stable. The clinical validity of the qualitative MSI designation has not been established. TMB is reported as mutations per megabase (mut/Mb). TMB may differ across specimens (e.g., primary versus metastatic, tumor content) and targeted panels. The TMB calculation will increase or decrease depending on: Size and region used to calculate TMB Percentage of tumor in the sample Germline variant filtering method Read depth and other bioinformatic test specifications Performance of OmniSeq INSIGHT has not been established for the detection of insertions and deletions larger than 25 base pairs. A negative result does not rule out the presence of a mutation below the limits of detection of the assay. The variant allele frequency (VAF) associated with each alteration is for informational use only and should not be used to make any quantitative clinical assessment. View more

Is proficiency testing performed for this test? Help
No