NGS-Based In Vitro Diagnostic Device Approved by FDA for Colorectal Cancer

The FDA has approved a 648-gene next-generation sequencing panel xT CDx as a companion diagnostic for determining microsatellite instability (MSI) status in those diagnosed with colorectal cancer (CRC), according to a press release from Tempus.¹

The xT CDx includes several necessary checkpoints to monitor performance and ensure that only high-quality data are gathered, such as DNA extraction, library preparation, hybridization capture, and sequencing.

The test was designed to identify substitutions, multi-nucleotide variants, insertion and deletion alterations, and MSI status in the aforementioned genes via DNA isolated from formalin-fixed paraffin-embedded tumor tissue samples. Moreover, DNA isolated from matched normal blood or saliva specimens from patients diagnosed with a solid malignant neoplasm can also be used.

xT CDx should be able to help identify patients with CRC who could benefit from treatment with targeted therapies such as cetuximab (Erbitux) in KRAS wild-type CRC in the absence of mutations in codons 12 or 13 and panitumumab (Vectibix) in KRAS wild-type CRC with the absence of mutations in exons 2, 3, or 4 and NRAS wild-type disease with absence of mutations in exons 2, 3, or 4.²

“This is a significant milestone for Tempus as we continue to establish a regulatory pathway for our platform, which offers solutions to advance both clinical care and support cutting-edge research,” Eric Lefkofsky, founder and chief executive officer of Tempus, said in a press release. “We designed xT CDx to be a smart test that can empower physicians to provide personalized care for their patients and support researchers in developing better therapeutics.”

Of 416 samples, a total of 164 were found to have at least 1 reported variance in an overlapping hotspot region, according to findings from a hotspot concordance analysis. A total of 214 base pairs were included in the intersection of the defined hotspot regions. Additionally, a total of 192 reported variants from both xT CDx and OM were assessed, including 187 substitutions across 10 genes and 5 insertions and deletions across 4 genes.

Additionally, detection of specific KRAS and NRAS CDx variants in 69 CRC samples were assessed. Of 31 CDx variants that were identified via the orthogonal methods (OM), 31 were detected by xT CDx; this translates to a positive percentage agreement of 100.0% (95% CI, 88.8%-100.0%). Moreover, cT CDx identified 648 negative variants of 649 that were identified by the OM, totaling a negative percentage agreement of 99.8% (95% CI, 99.1%-100.0%).

When MSI status was assessed using xT CDx vs immunohistochemistry (IHC) staining, 110 samples were identified as being MSI high with xT CDx of 117 samples that were positive by IHC staining. This translated to a positive percentage agreement of 94% (95% CI, 88%-98%). The newly approved test also identified 195 microsatellite stable samples of 199 that were identified via IHC. This translated to a negative percentage agreement of 98% (95% CI, 95%-99%).

The assay includes several necessary checkpoints to monitor performance and ensure that only high-quality data are gathered. This includes DNA extraction, library preparation, hybridization capture, and sequencing.

References

1. Tempus Receives U.S. FDA Approval for xT CDx, a NGS-Based In Vitro Diagnostic Device. News release. Tempus. May 1, 2023. Accessed May 1, 2023. https://bit.ly/3p124gA
2. cT CDx Technical Information. Tempus. February 2023. Accessed May 1, 2023. https://bit.ly/3VsYCr1