TEST:

Oncomap™ ExTra test

The results of the Ames test and Allium cepa test were statistically significant compared to the controls (p < 0.05), as determined by the Mann-Whitney test for genotoxicity and cytotoxicity. Thus, the results of the present study indicate possible environmental contamination and a potential risk to the health of miners, which suggests that further studies are important in the region.

The Oncomap ExTra assay allowed identification of both commonly observed and rare TERT promoter mutations, including a fusion, in 78.9% of bladder cancer patients. Such assays are useful to identify both TERT alterations prognostic for progression and patients eligible for clinical trials evaluating TERT-directed therapies. In addition, TERT mutations may be associated with FGFR3 mutations and high TMB, which have matched therapies, though these associations need to be validated in an independent cohort.

In addition to TMPRSS2:ERG, the Oncomap ExTra assay identified several low frequency ETS fusions, all of which could be used to assist patients and physicians to select appropriate treatments. The identification of ETS fusions appears to be limited when using only DNA sequencing. Oncomap ExTra RNA analysis identified 66 additional fusions, representing almost 30% of those present, not identified by whole-exome DNA sequencing, suggesting RNA plus DNA assays detect fusions more reliably than DNA-only assays.

Although the findings are preliminary due to limited case numbers, the identification of these mutations may be a useful adjunct to the diagnosis of barnaculate carcinoma. Additional studies including more cases will be needed to validate the study results and identify tumorigenic roles and clinical significance of these mutations.

"Protocol#: NSABP C-14 / ES 16-002. Support: NSABP Foundation, ExactSciences Clinical trial information: 05210283."

Up to 30 patients will be enrolled to each CRC cohort from approximately 8 sites in the US and will receive 3 mg/kg navicixizumab alone (Cohort A1) or in combination with irinotecan (180 mg/m2 on Days 1 and 15 of a 28-day cycle, Cohort A2). Secondary efficacy endpoints include overall survival, time to response, disease control rate, duration of response, and the relationship between antitumor activity of navicixizumab and Xerna TME Panel biomarker subtypes. Clinical trial information: NCT05453825.

Wnt signaling is activated in about half of all GI cancers, and APC alterations are the most frequently observed. Whole transcriptome profiling allowed us to identify RSPO2/3 fusions, which also contribute to activation of the Wnt pathway. Wnt activation appears to be a particularly important in CRC, with 81.1% of CRC having a Wnt pathway alteration.

The combination of dabrafenib plus trametinib was recently FDA-approved for use in these BRAF V600E altered unresectable or metastatic cancers. Analysis of whole-exome and whole transcriptome sequencing data found actionable BRAF mutations in 4.4% of GI cancer patients, 37.6% of whom had BRAF mutations not at V600. Several biomarkers were significantly associated with BRAF alterations. Assays that are limited to DNA sequencing, or to targeted gene panels, may not detect mutations and fusions that could aid in therapy selection and prognosis.

"Exact Sciences Corp...announced that new data presentations supporting the clinical value of its Precision Oncology portfolio will be shared in ten abstracts and three presentations at the 2022 San Antonio Breast Cancer Symposium (SABCS). The data presented highlight the Oncotype DX Breast Recurrence Score test, Oncomap ExTra test, a new investigational test to predict radiation therapy benefit, and an initial look at Exact Sciences' tumor-naive minimal residual disease (MRD) approach."

Eligible TNBC patients will have locally advanced or metastatic disease and have received at least 2 and no more than 4 prior lines of standard therapy for metastatic disease, including immunotherapy (for PD-L1 positive TNBC patients), and sacituzumab govitecan...Up to 30 patients will be enrolled to each TNBC cohort from approximately 8 sites in the US and will receive 3 mg/kg navicixizumab alone (Cohort C1) or in combination with paclitaxel (80 mg/m2 on Days 1, 8, and 15 of a 28-day cycle) (Cohort C2)...Cohort continuation and future evaluation decisions will be guided by the boundaries identified by a sequential monitoring procedure. Secondary efficacy endpoints include overall survival, time to response, disease control rate, duration of response, and the relationship between antitumor activity of navicixizumab and Xerna TME Panel™ biomarker subtypes.

Table 1. Biomarkers that showed the highest association with ESR1 and other notable breast cancer biomarkers.

"Exact Sciences Corp...announced new data supporting its cancer tests and treatment guidance tools will be showcased in nine poster presentations and five e-abstracts at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, being held June 3-7 in Chicago, Illinois...The analyses support use of Oncomap™ and Oncomap™ ExTra, comprehensive genomic profiling tests formerly known as the Oncotype Map™ Pan-Cancer Tissue and GEM ExTra® tests, respectively, to inform targeted therapy selection and clinical trial options for patients with advanced solid tumors."

Our study found I-O sensitive BMs in common and in rare aggressive cancers. The GEM ExTra assay can stratify cancer patients for likely responsiveness to immunotherapy. >

"Exact Sciences...and OncXerna Therapeutics...announced today they have entered an exclusive license agreement to bring OncXerna's Xerna TME Panel lab services to more U.S. patients. The Xerna TME (tumor microenvironment) Panel is an innovative gene expression score that helps identify patients likely to respond to anti-angiogenic and immunotherapies. The agreement allows Exact Sciences to provide more critical answers to cancer patients and physicians facing difficult therapy selection decisions supporting biopharma partners in patient selection for their therapeutic programs."

In depth examination of this large cohort suggests that IR resulting from AS events occur frequently within RCC. Further efforts to investigate the association of AS events and clinical outcomes are underway.

GEM ExTra demonstrated analytic specificity (PPV) of > 99.9% and analytic sensitivity of 98.8%. Application of GEM ExTra to 1,435 patient samples revealed clinically actionable alterations in 83.9% of reports, including 31 (2.5%) where therapeutic recommendations were based on RNA fusion findings only.

Although the majority of GAs identified were concordant, each platform exclusively identified GAs with varying clinical significance. SOX4 and E2F3 mutation, shown to correlate with invasive potential in bladder cancer, were detected exclusively on WES. In contrast, RBM and CHEK2 (of known significance in melanoma and breast cancer) were found exclusively on TS.

By identifying a correlation between radiomic features of TERT mutation in primary tumors and BAP1 mutation in metastatic sites, our work may ultimately yield a non-invasive method of discerning mutational status in patents with mRCC. Efforts are ongoing to validate our findings within The Cancer Imaging Archive.

Our study confirms that ctDNA and tissue-based genomic profiling continue to provide consistently high levels of agreement. Notably, the percentage of samples with ≥1 ctDNA alteration detected was significantly lower in both cohorts compared to previous studies in RCC. More shared alterations were found on ctDNA when both ctDNA and tissue-based assessment were obtained at closer intervals.

Our study confirms that ctDNA and tissue-based genomic profiling continue to provide consistently high levels of agreement. Notably, the percentage of samples with ≥1 ctDNA alteration detected was significantly lower in both cohorts compared to previous studies in RCC. More shared alterations were found on ctDNA when both ctDNA and tissue-based assessment were obtained at closer intervals.