xM and xM NeXT Personal Dx Assays Now Available for MRD Testing in Cancer

Halla Nimeiri, MD

The tumor-naive xM assay and the tumor-informed xM NeXT Personal® Dx assay are now available for clinical use in detecting residual disease and early cancer recurrence, and for monitoring immunotherapy treatment response in patients with cancer.¹

xM is a rapid, tumor-naive, plasma-based test intended to detect circulating tumor DNA (ctDNA) in the blood of patients with early-stage colorectal cancer (CRC) following curative-intent surgery. The assay is designed to accurately classify tumor fragments from non-tumor fragments to improve the precision of minimal residual disease (MRD) testing.

NeXT Personal Dx is an ultra-sensitive, tumor-informed MRD and monitoring test that can identify up to 1800 somatic variants unique to a patient’s tumor to inform individualized treatment decision-making. The assay can detect small traces of ctDNA in the blood of patients with early-stage non–small cell lung cancer (NSCLC) and breast cancer following curative intent treatment. Additionally, NeXT Personal Dx can also be used for immunotherapy monitoring for patients with late-stage solid tumors.

“MRD testing is the perfect complement to our comprehensive testing portfolio, as we are now equipping physicians with a proactive solution that provides early-stage cancer insights for their patients that is critical to their care,” Halla Nimeiri, MD, chief development officer at Tempus, stated in a news release. “We believe it is important to offer a portfolio of both a rapid, tumor-naive test and an ultra-sensitive, tumor-informed test so that physicians have optionality in addressing each of their patient’s specific needs.”

At the 2024 ASCO Annual Meeting, investigators presented data from a subgroup analysis of the GALAXY study (UMIN000039205) in the CIRCULATE-Japan platform evaluating the longitudinal clinical performance of the tumor-naive xM assay in patients with resected stage II or III CRC.²

Findings showed that the assay exhibited a longitudinal sensitivity of 83.3% (95% CI, 67.2%-93.6%) and a longitudinal specificity of 89.5% (95% CI, 75.2%-97.1%) among all evaluable patients with CRC (n = 74). In patients with stage II disease, the longitudinal sensitivity was 91.7% (95% CI, 61.5%-99.8%) and the longitudinal specificity was 88.2% (95% CI, 63.6%-98.5%). In patients with stage III CRC, these rates were 79.2% (95% CI, 57.8%-92.9%) and 90.5% (95% CI, 69.6%-98.8%), respectively.

Notably, data also showed that xM ctDNA status was a stronger prognostic biomarker for disease-free survival (adjusted HR, 9.69) compared with standard-of-care carcinoembryonic antigen (adjusted HR, 2.13).

Among evaluable patients (n = 30), xM demonstrated a mean lead time of 4.66 months from time of first MRD-positive test to disease recurrence or death. In patients who underwent surgery only (n = 22), this mean lead time was 5.62 months.

To conduct the subgroup analysis, investigators randomly selected 80 patients from the observational GALAXY trial. Selection was based on recurrence to 50% with the intention of maintaining the ratio of patients with stage II or III recurrent or non-recurrent CRC observed in GALAXY. Sixty-nine patients were evaluable for the landmark timepoint (LMT) analysis, and 74 were included in the longitudinal analysis. LMT was defined as 4 weeks following surgery for patients with pathological stage II or III CRC.

The xM MRD assay was used to analyze residual plasma samples, and MRD calls were blinded to clinical outcomes. The longitudinal sensitivity and specificity of xM were based on the LMT sample and all evaluable longitudinal samples, which were collected once every 3 months after surgery for 24 months, or until recurrence or death.

Additional data from the LMT analysis showed the sensitivity and specificity for all patients was 61.1% (95% CI, 43.5%-76.9%) and 87.9% (71.8%-96.6%), respectively. In patients with stage II CRC, the LMT sensitivity was 64.3% (95% CI, 35.1%-87.2%), and the specificity was 93.3% (95% CI, 68.1%-99.8%). For patients with stage III disease, the LMT sensitivity and specificity were 59.1% (95% CI, 36.4%-79.3%) and 83.3% (95% CI, 58.6%-96.4%), respectively.

References

1. Tempus announces the clinical launch of its MRD testing portfolio. News release. Tempus. May 31, 2024. Accessed June 3, 2024. https://www.tempus.com/news/tempus-announces-the-clinical-launch-of-its-mrd-testing-portfolio/
2. Nakamura Y, Kaneva K, Lo C, et al. Longitudinal clinical performance of a novel tumor-naive minimal residual disease assay in patients with resected stage II and III colorectal cancer: a subset analysis from the GALAXY study in CIRCULATE-Japan. J Clin Oncol. 2024;42(suppl 16):3618. doi:10.1200/JCO.2024.42.16_suppl.3618