TEST:

Tempus xF+ Panel

PDAC disease biology is still poorly understood, and the effect of many genetic mutations it harbors are yet to be elucidated. The identification of multiple VUS through NGS reinforces the need for continued genetic testing to discover novel biological pathways, personalize therapy, and improve survival. In particular, it will be worth exploring how different KMT2C (MLL3) variants affect PDAC progression, and whether increased KMT2C (MLL3) VUS in AA patients can help corroborate racial variations in genetic and epigenetic regulation of PDAC.

"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."

Our preliminary analysis of gene mutations in liquid biopsy samples obtained from patients in the ongoing 1801 Part 3B phase 2 trial identified potential predictive biomarkers of clinical outcome in mPDAC patients treated with combination of elraglusib/GnP. Clinical trial information: NCT03678883.

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.

"Tempus...announced a brand-new multi-omics collaboration with Actuate Therapeutics, Inc...to support its ongoing Phase 1/2 Study of elraglusib, formerly known as 9-ING-41 (NCT03678883). The Tempus’ xF+ liquid biopsy and Research Use Only (RUO) DNA methylation tests will be used to help discover and further validate biomarker profiles in patients who may benefit from treatment with elraglusib, a selective GSK-3β inhibitor."

"Tempus...announced the expansion of its comprehensive genomic profiling offerings with xF+, a new non-invasive, liquid biopsy panel of 523 genes, focused on pathogenic mutations in cell-free DNA (cfDNA). The test will originally be available on a limited basis alongside xF, Tempus’ 105-gene liquid biopsy assay, with a broader launch slated for later this year."

"In the largest study of its kind, we show that dual tumor tissue and ctDNA testing—with samples collected either concurrently or longitudinally—identified more patients with actionable alterations than single modality testing alone and therefore should be considered as part of routine NGS testing. Additional studies to explore the genetic and intra-patient tumor heterogeneity of these variants as well as the impact of time between tissue and plasma sampling assessments and implications for timing of therapeutic recommendations are underway."

ctDNA testing is a reliable method to detect DNA damage repair LOF alterations but is limited to alterations and genes/exons covered by the ctDNA test. CH alterations are frequent, especially for ATM, thus matched normal analysis is preferred. Changes in ctDNA as early as 3 wks were associated with improved outcomes and may be useful for evaluating drug activity in heterogenous tumors outside of traditional efficacy endpoints.

CDH1 mutations, which are associated with familial gastric cancers and more aggressive disease, were present in 33% of Hispanic patients with gastric adenocarcinoma in our study. Nearly half of these identified patients were younger than 50 years old. The high frequency of CDH1 mutations may contribute to the unique pathogenesis of gastric cancers in Hispanic patients.