NGS-Based xT CDx Test Is Now Commercially Available in United States for Solid Tumor Profiling

The next-generation sequencing (NGS)–based in vitro diagnostic device, xT CDx, is now available nationwide in the United States for use in solid tumor profiling.1

In May 2023, the FDA approved xT CDx, a 648-gene NGS assay, for solid tumor profiling, including microsatellite instability status and companion diagnostic claims for patients with colorectal cancer (CRC).2

“We are thrilled to broadly introduce our xT CDx test, which combines the trusted performance our clinicians rely on, now with FDA approval,” Ezra Cohen, MD, chief medical officer of Oncology at Tempus AI, stated in a news release.1 “Tempus has an unwavering commitment to providing high-quality and robust assays, so clinicians have the most comprehensive and actionable insights in a timely manner. This is consistent with the goal of improving the outcomes for all of their patients, and we look forward to providing xT CDx nationally to make that possible.”

The in vitro diagnostic device uses DNA isolated from FFPE tumor tissue samples and DNA isolated from matched normal blood or saliva samples derived from patients diagnosed with solid malignant neoplasms in order to detect substitutions—such as single nucleotide variants (SNVs) and multi-nucleotide variants (MNVs)—and insertion/deletion alterations in 648 genes.

Additionally, xT CDx is approved as a companion diagnostic to identify patients with KRAS wild-type CRC who could be candidates for treatment with cetuximab (Erbitux); and patients with KRAS and NRAS wild-type CRC who may be candidates for treatment with panitumumab (Vectibix).3

The ability of xT CDx to detect alterations was compared with an externally validated orthogonal method (OM); researchers compared SNVs, MNVs, insertions, and deletions detected by xT CDx and the OM from 416 samples spanning 31 different tumor types.

Tumor types included CRC (n = 69), breast cancer (n = 44), ovarian cancer (n = 38), glioblastoma (n = 34), non–small cell lung cancer (n = 29), endometrial cancer (n = 26), clear cell renal cell carcinoma (n = 22), bladder cancer (n = 18), melanoma (n = 17), pancreatic cancer (n = 14), thyroid cancer (n = 12), low-grade glioma (n = 12), sarcoma (n = 10), tumor of unknown origin (n = 8), meningioma (n = 7), prostate cancer (n = 7), gastrointestinal stromal tumor (n = 7), endocrine tumor (n = 6), gastric cancer (n = 5), head and neck squamous cell carcinoma (n = 4), kidney cancer (n = 3), brain cancer (n = 3), small cell lung cancer (n = 3), biliary cancer (n = 3), cervical cancer (n = 3), esophageal cancer (n = 3), oropharyngeal cancer (n = 2), liver cancer (n = 2), head and neck cancer (n = 2), mesothelioma (n = 2), and adrenal cancer (n = 1).

Notably, since OM utilized only tumor samples, the use of tumor samples and patient-matched normal samples with xT CDx led to the reclassification of 148 variants to germline alterations after being labeled as somatic by the OM.

Investigators also evaluated concordance in hotspot and non-hotspot regions, identifying the positive percent agreement (PPA) and negative percent agreement (NPA) for each variant.

Among the 416 samples analyzed, 164 featured at least 1 reported variant in an overlapping hotspot region. A total of 214 base pairs were at the intersection of the defined hotspot regions of both the xT CDx and OM targeted regions.

In total, 192 variants in hotspots reported with both assays were assessed, including 187 substitutions across 10 genes and 5 insertions or deletions across 4 genes. The PPA and NPA for all variants were 98.9% (95% CI, 96.2%-99.9%) and 100.0% (95% CI, 100.0%-100%), respectively.

The detection of specific KRAS and NRAS CDx variants was also examined in CRC samples. The 31 CDx variants were identified in both the OM and xT CDx, and 648 of the 649 CDx variants deemed negative by the OM were identified as negative by xT CDx. These results translated to a PPA of 100% (95% CI, 88.8%-100.0%) and an NPA of 99.8% (95% CI, 99.1%-100.0%).

References

1. Tempus announces the national launch of FDA-approved xT CDx test. News release. Tempus AI. January 15, 2025. Accessed January 15, 2025. https://www.tempus.com/news/pr/tempus-announces-the-national-launch-of-fda-approved-xt-cdx-test/
2. Tempus receives US FDA approval of xT CDx, a NGS-based in vitro diagnostic device. News release. Tempus AI. May 1, 2023. Accessed January 15, 2025. https://www.tempus.com/news/tempus-receives-u-s-fda-approval-for-xt-cdx-a-ngs-based-in-vitro-diagnostic-device/
3. xT CDx technical information. Tempus AI. August 2024. Accessed January 15, 2025. https://www.tempus.com/wp-content/uploads/2024/10/Tempus-xT-CDx_Technical-Information.pdf