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Tempus xF Assay

We report herein real-world and preclinical evidence that ESR1 mutations, particularly Y537S and D538G, can drive resistance to CDK4/6 inhibitors.

These findings require external validation, particularly using different ctDNA panels. Further research is needed to elucidate the biological mechanisms underlying the association between specific mutations and VTE risk in cancer patients.

In this study, we analyzed a subset of patients from the Dallas Metastatic Breast Cancer Study comprised of patients with HR+, HER2 non-amplified, mBC who underwent treatment with a CDK4/6 inhibitor (palbociclib, ribociclib, abemaciclib) and ET, became resistant to therapy, and had ctDNA testing (n=102). There is an urgent need to develop predictive biomarkers that capture real-time changes in tumor biology. Tissue analyses from patients resistant to CDK4/6 inhibitors have demonstrated a 14%-28% expression of CCNE1, 16% of MYC mutations, and 9%-10% expression of RB mutations. In our study, we observe a lower rate of detection in ctDNA of each gene.

Further research is warranted to elucidate how longitudinal ctDNA analysis can delineate biomarkers of response and resistance at both the mutation and ctDNA fraction levels. Understanding these dynamics could offer valuable insights into disease progression and guide personalized treatment strategies for RCC patients.

"Guardant Health filed a lawsuit...against rival cancer genomics firm Tempus AI, alleging that Tempus has infringed a handful of its patents relating to liquid biopsy sequencing methods...Guardant specifically cited Tempus' Tempus xF, Tempus xF+, and Tempus xM Monitor assays as examples, as well as the firm's recently developed minimal residual disease offering, Tempus xM MRD."

"In this retrospective analysis, Tempus EHR integrations increased ordering of comprehensive NSCLC NGS by 53%. Despite study limitations such as the incomplete resolution into internal alternate sequencing workflows, this large-scale analysis provides further evidence that EHR-based workflow improvements reduce the barrier to appropriate sequencing."

70% of patients received Trastuzumab deruxtecan (T-DXd) and 30% received Sacituzumab govitecan (SG). In HR+ mBC, detection of mutated genes associated with the Ras-MAPK pathway by ctDNA was associated with a more favorable response when treated with ADCs. These findings are exciting because HR+ BCs are being targeted with ADCs regardless of HER2 or TROP2 expression, highlighting the need for new biomarkers to distinguish which HR+ patients to treat. Our retrospective analysis findings are limited by the number of patients with ctDNA testing and also timing of testing.

This analysis shows that ctDNA profiling is complementary to tissue based NGS in RCC and can increase the detection of mutations. Concordance between ctDNA and tissue profiling increased in individuals with metastatic disease. Future research is warranted to understand how longitudinal ctDNA analysis can define biomarkers of response and resistance at the mutation and ctDNA fraction levels.

"A novel classifier trained on multiple orthogonal bioinformatics features can reliably distinguish CH from tumor-derived variants using only liquid biopsy data with high accuracy, including high sensitivity and high specificity."

xF monitor can be used as a strategy to identify patients at a high risk of progression who could benefit from early switch or intensifying therapy. Results need to be prospectively validated in a larger cohort.

Patients with ESR1m acquired on AI may retain treatment response if switched to selective estrogen receptor degraders (SERDs) like fulvestrant... xF Monitor is a ctDNA assay that tracks changes in quantitative ctDNA TF and simultaneously monitors for the emergence of ESR1m, providing a diagnostic that identifies resistance to AI therapy and enables early switch to therapies that could improve outcomes in a patient population with poor prognosis. A larger prospective clinical study is needed to validate these findings.

Here we introduce a novel sensitive and specific tumor-informed, non-bespoke approach for estimating ctDNA TF. Linearity improves with increased panel size and increased variant number. These results suggest that a tumor-informed ctDNA TF can be utilized to improve the sensitivity of existing methods for estimating tumor fraction to help in treatment decisions using Tempus' tissue and liquid comprehensive NGS genomic profiling platform.