TEST:

PredicineBEACON™

ctDNA was assessed using the PredicineBEACON assay, that interrogates up to 50 personalized tumor variants and 500 hot-spot mutations, in 3 mL archived plasma isolated from EDTA tubes collected post-NAC but before surgery from 44 patients with stage I/III triple negative breast cancer (TNBC) who received durvalumab and weekly nab-paclitaxel followed by doxorubicin/cyclophosphamide on a clinical trial (NCT02489448). There was significant decrease in methylation signal in post-compared to pre-NAC samples, but post-treatment methylation signal was lower in cases with pCR vs RD. Post-NAC plasma tumor fraction and change in tumor-derived methylation signal predict the extent of RD and recurrence in TNBC patients.

Detection and monitoring of utDNA MRD proved feasible in this initial investigation in BCG-unresponsive NMIBC patients treated with durvalumab containing regimens. Post-treatment utDNA MRD was detected in most samples. Post-treatment reduction of utDNA tumor fraction was associated with durable clinical benefit.

Nearly all patients with BCG unresponsive CIS begin salvage therapy MRD + and have a quantifiable decline in TF with treatment. We identify genomic alterations previously reported with immune escape and actionable mutations in DNA damage repair and the FGFR3 pathway, now targetable with intravesical therapy.

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.

"Predicine, Inc...announced today that it will present data from 9 ctDNA studies at ASCO 2024, spotlighting the clinical utility of Predicine’s genomic and epigenomic liquid biopsy solutions for patient selection, disease monitoring, and drug resistance mechanism studies. The forthcoming data represents significant potential for the practical application of Predicine’s cutting-edge liquid biopsy technology in personalized cancer care, clinical trials, and Companion Diagnostic (CDx) development."

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.

"Predicine...announced today that it will present data from 15 ctDNA studies at AACR 2024, spotlighting the clinical utility of Predicine’s genomic and epigenomic liquid biopsy solutions for patient selection, disease monitoring, and disease mechanism studies."

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.

Furthermore, DNA methylation abnormality scores correlated positively with mutation-based tumor fractions (r = 0.62), with higher grade samples showing a stronger correlation (r = 0.81; n = 13) than lower grade samples (r = 0.54; n = 17).ConclusionWe demonstrate the utility of methylation patterns extracted ucfDNA samples obtained prior to reTURBT to detect and monitor NMIBC. Urinary DNA methylation patterns were highly concordant with clinical pathology status and as well as tumor fractions determined from mutation analysis.

P1 | N=498 | NCT04449874 | Sponsor: Genentech, Inc. | "Consistent with the outcomes of the prior Phase 1 clinical trial, PredicineBEACON showcased remarkable biomarker results in the Phase 1b clinical trial of Divarasib Plus Cetuximab in CRC patients. A decline in KARAS G12C variant allele frequency was associated with treatment response, observed as early as CID15 in responsive patients. Using baseline, on-treatment, and end-of-treatment plasma samples, out of the 14 patients profiled, 13 (92.9%) exhibited at least one acquired genomic alteration linked with treatment resistance. The enhanced antitumor activity observed in this study reinforces the clinical utility of liquid biopsy profiling in evaluating the Phase 1b clinical trial of combined therapy in CRC patients."

This study demonstrated the clinical utility of ctDNA MRD assay in patients with resectable HCC, as notably evident in the robust detection of MRD using plasma samples collected 7 days after surgery. Furthermore, the assessment of post-surgical MRD status provided valuable prognostic insights into both patient survival and the risk of disease relapse. ctDNA MRD status played a pivotal role as a prognostic differentiator, particularly among clinically low-risk patients.