TEST:

PredicineWES+™

PredicineWES+ is a comprehensive assay for detecting cancer variants in blood and urine. It detects mutations across 600 cancer-related genes at a 20,000x sequencing depth, with cfDNA mutation profiles that align closely with public tissue datasets. PredicineWES+ is utilized for baseline profiling in the PredicineBEACON MRD assay and demonstrates a high correlation in TMB scores with PredicineATLAS.

In this study, we observed no significant difference in clinical outcomes between bladder cancer patients receiving bladder preservation or surgery-based intervention. Urine and blood-based MRD tests closely correlated with clinical outcomes. Our study emphasizes the value of serial monitoring of urine/plasma-based MRD assays in informing MRD status or treatment response for patients who undergo bladder preservation or cystectomy.

Minimal residual disease can be detected using utDNA prior to rTURBT with high accuracy, making this a promising urinary biomarker. If validated, the combined approach using CNB and tf from utDNA for the detection of MRD can be used to predict patients in need of maximal resection prior to starting intravesical therapy.

Urinary tumor DNA holds promise for detecting MRD prior to rTURBT. Tissue informed probes with ultra-deep sequencing improve detection of MRD where other biomarkers have fallen short. CNB independently performed excellently in detecting residual disease and combining tf with CNB may further optimize test performance.

The established subclonal deconvolution pipeline enhances biomarker analysis from assays utilizing WES with boosted sequencing depth for selected genes.

Analysis of the mutational profile of pBT and pNMIBC revealed differential patterns of somatic mutations. Many expected gene mutations were detected in pNMIBC, but surprisingly 18% of all mutated genes were shared between tumor and pathologically benign samples. The fact that only one somatically mutated gene was exclusive to pBT signifies excellent censoring of variants by the DeepSea algorithm.

Index and reTURBT tumor tissue have high variant concordance, demonstrating the rationale in utilizing tumor informed ucfDNA assays to identify residual disease prior to repeat transurethral resection. Novel mutations also arise in almost all patients highlighting the potential utility of personalized MRD tracking prior to reTURBT. We demonstrate that urinary TF derived from LPWGS of ucfDNA currently provides moderate sensitivity to detect disease prior to reTURBT.

"Predicine...announce its participation in the European Society for Medical Oncology (ESMO) 2023 Congress in Madrid, Spain. The company will present six compelling poster studies, unveiling the future of liquid biopsy solutions...These poster presentations will shine a spotlight on Predicine’s groundbreaking liquid biopsy innovations, including PredicineBEACON™, a revolutionary solution for personalized and actionable minimal residual disease (MRD) analysis."

"Predicine, Inc...announced a new study published in The New England Journal of Medicine (NEJM), demonstrating the clinical utility of its minimal residual disease (MRD) Liquid Biopsy Assay in support of Genentech's Phase 1 Clinical Trial of Divarasib. This milestone reaffirms Predicine's position as a leader in the field of liquid biopsy diagnostics....These findings underscore the clinical utility of liquid biopsy profiling in the assessment of phase I clinical trial of Divarasib."

Besides its convenience in sample collection, urine-based genomic profiling also has the potential to capture more heterogeneity of urinary tract malignancies as compared to tissue or blood based testing alone. Urine ctDNA monitoring is a useful complementary test to support standard tissue and plasma based assays in high risk bladder and UTUC patients.

Urinary tumor DNA shows promise as a surrogate for minimal residual disease and may predict TURBT pathology for NMIBC. Genomic alterations between index and rTURBT tumors are highly concordant in papillary tumors even in the setting of upstaging, which may aid in targeted intravesical or systemic therapy selection. Larger cohorts and long-term follow up is needed to determine if utDNA can risk-stratify patients prior to rTURBT and predict long-term recurrence.

Our results demonstrate the feasibility of using an ultra-sensitive, baseline-informed MRD assay to detect strong correlations between MRD status and prognosis outcomes in peri-surgical plasma samples collected as early as 7 days post-surgery in resectable HCC patients. This study highlights the clinical utility of MRD testing in peri-surgical settings.

Genomic alterations between index and re-TUR lesions are highly concordant even when pathologic upstaging occurs. However, index lesions harbored unique mutations in cell cycle and immune checkpoint genes. Surface tumor cells may behave differently than base tumor cells, with varying therapeutic targets.

Finally, serial analysis of plasma cfDNA demonstrated an increase in ctDNA TF and cancer variants, preceding evidence of radiographic and clinical disease progression in many patients.Conclusion We conducted a comprehensive concordance study to infer cfDNA TF using PredicineWES+ and PredicineCNB in more than 300 patient samples. Our study demonstrated its clinical utility where the integrated TF analysis may provide a more robust and accurate estimation of disease burden in cancer patients.

Urinary tumor DNA shows promise as a surrogate for minimal residual disease and may predict TURBT pathology for NMIBC. Genomic alterations between index and rTURBT tumors are highly concordant in papillary tumors even in the setting of upstaging, which may aid in targeted intravesical or systemic therapy selection. Larger cohorts and long-term follow up is needed to determine if utDNA can risk-stratify patients prior to rTURBT and predict long-term recurrence.

Urinary tumor DNA shows promise as a surrogate for minimal residual disease and may predict TURBT pathology for NMIBC. Genomic alterations between index and rTURBT tumors are highly concordant in papillary tumors even in the setting of upstaging, which may aid in targeted intravesical or systemic therapy selection. Larger cohorts and long-term follow up is needed to determine if utDNA can risk-stratify patients prior to rTURBT and predict long-term recurrence.

Table: 108P Conclusions Our results suggest that deletions are preferentially selected during the development of treatment resistance to ET + CDK4/6i. As our previous study demonstrated that increasing bCNB levels precede radiographic detection of progression in approximately two-thirds of patients, LP-WGS may constitute a low-cost approach to detect these events through serial blood monitoring during treatment.

Conclusions This study demonstrated the technical feasibility of analyzing genome-wide copy number variations and somatic variants using CSF samples from patients with NSCLC leptomeningeal metastases. Furthermore, this study revealed the comprehensive mutational landscape of NSCLC leptomeningeal metastases, providing novel biomarkers for clinical diagnosis and drug resistance mechanism study in NSCLC.

Conclusions This study demonstrates the effectiveness of urinary tumor DNA as a tissue surrogate for mutation profiling in MIBC at the whole-exome scale, supporting urine-based noninvasive molecular profiling in precision medicine for patients with bladder cancer. PredicineWES+ assay enables accurate detection of subclonal mutations from urine samples and enables the detection of urine-based personalized minimal residual diseases (MRD) in MIBC.