Fig 1.
CAP = College of American Pathologists; CDx = companion diagnostic; CLIA = Clinical Laboratory Improvement Amendments; DNA = deoxyribonucleic acid; FDA = United States Food and Drug Administration; FFPE = formalin-fixed, paraffin-embedded.
Table 1.
F1CDx companion diagnostic claims.
Table 2.
Clinical validity of F1CDx via non-inferiority for companion diagnostic claims.
Table 3.
Clinical utility of F1CDx in each efficacy analysis population.
Table 4.
Clinical utility of F1CDx for determining TMB-H status (≥10 mut/Mb) in solid tumors in the efficacy analysis population.
Table 5.
Clinical utility of F1CDx for BRCA1/2 alteration companion diagnostic claims.
Table 6.
Clinical utility of F1CDx for HRR mutations companion diagnostic claims in the combined Cohort A and Cohort B.
Table 7.
Sample validation for F1CDx companion diagnostic claims.
Table 8.
Sample validation for F1CDx companion diagnostic claims.
Fig 2.
LoD ranges for (A) SVs and (B) amplifications and rearrangements a LoD calculations for the platform variants were based on the hit rate approach for variants with less than three levels with hit rate between 10% and 90% and probit approach for variants with at least three levels with hit rate between 10% and 90%. LoD from the hit rate approach is defined as the lowest level with 95% hit rate (worst-case scenario). b Data includes an alteration in the TERT promoter, 124C>T (LoD of 7.9%). TERT is the only promoter region interrogated and is highly enriched for repetitive context of poly-Gs, not present in coding regions. c Alterations classified as “known” are defined as those that are listed in COSMIC. d Alterations classified as “other” include truncating events in tumor suppressor genes (splice, frameshift, and nonsense) as well as variants that appear in hot-spot locations but do not have a specific COSMIC association or are considered VUS due to lack of reported evidence and conclusive change in function. e Sensitivity calculations for the platform variants were based on the hit rate approach for variants with less than three levels with hit rate between 10% and 90% and probit approach for variants with at least three levels with hit rate between 10% and 90%. LoD from the hit rate approach is defined as the lowest level with 95% hit rate (worst-case scenario). f Max represents VUS alteration at calling threshold. bp = base pair; CN = copy number; Mb = megabase; MSI = microsatellite instability; mut = mutation; TMB = tumor mutation burden; VUS = variants of unknown significance.
Fig 3.
LoDs per driver status (known, likely and unknown) for SUBs using the hit rate approach.
LoD = limit of detection.
Table 9.
Reproducibility of platform-wide variant detection.
Table 10.
Reproducibility of companion diagnostic alterations.
Table 11.
Concordance of F1CDx and an externally validated NGS assay for platform-wide variants and CDx biomarkers.
Table 12.
Concordance of F1CDx and an externally validated WES for TMB-High with ≥10 mut/Mb as cut-off.
Table 13.
Concordance of F1CDx and FoundationOne® for platform-wide variants.
Fig 4.
Frequencies of targetable known/likely rearrangements in common tumor types detected by F1CDx between 2018 and 2020.
Source: from over 504,000 Foundation Medicine profiles consented for secondary research, 191,575 unique US patients tested with F1CDx from Jan. 14, 2018 through Mar. 31, 2021. CRC = colorectal cancer; NSCLC = non-small cell lung cancer.
Fig 5.
Growth and evolution of precision medicine therapies and companion diagnostic biomarkers over time, as demonstrated by increasing number of approved therapies included on Foundation Medicine test results and increasing number of companion diagnostic indications and biomarkers.
1 FoundationOne®CDx. Technical Information. Foundation Medicine, Inc; 2020. www.F1CDxLabel.com. 2 Data on File, Foundation Medicine, Inc., 2021. 3 FoundationOne®Liquid CDx. Technical Information. Foundation Medicine, Inc; 2020. www.F1LCDxLabel.com. Updated July 26, 2021. CDx = companion diagnostic.
Fig 6.
Frequency of F1CDx reports with potential therapeutic implications by disease group and definition of actionability: (A) therapy options available within the tumor type indicated; (B) therapy options available in tumor types other than the assigned indication; (C) disease groups with clinical trial options; and (D) disease groups with FDA approved companion/complementary diagnostics within the tumor type indicated. Source: 191,575 unique US patients tested with F1CDx and consented for secondary research from January 14, 2018 through March 31, 2021. All disease groups contain ≥100 specimens. Values indicate counts per disease group. CRC = colorectal cancer; CUP = cancer of unknown primary; GIST = gastrointestinal stromal tumor; NSCLC = non-small cell lung cancer; PNS = peripheral nervous system.