TEST:

Personalized Cancer Monitoring (PCM™)

PCM detected ctDNA in patients who relapsed with a long lead-time over clinical relapse, shows strong association with relapse-free survival and may be used to identify patients at high-risk for relapse, allowing for earlier intervention.

The combined detection of personalized tumor-specific alterations and HPV provides a highly sensitive approach for detecting low disease burden in early stage HPV-associated OPC patients before and during treatment.

Primary endpoint of this study is to evaluate the correlation between PCM test results at the landmark time point and the patient's 24 month recurrence risk. Secondary endpoints include evaluating the impact on patient outcomes attributable to MRD result-based changes to treatment and other forms of clinical management, correlating between PCM result at baseline time point and patient recurrence risk and outcomes and investigating the lead time of PCM positivity over clinical/imaging based evidence of recurrence

"The US District Court for the District of Delaware on Friday ordered that ArcherDx and Invitae permanently stop using products containing material patented by Natera, with certain exceptions."

Active enrollment started in December, 2022 and 21 pts with resectable PC and 64 pts with unresectable have been enrolled as of September 2023. Clinical trial information: NCT06043921.

Transcriptome analysis of sonicated and nonsonicated tumor tissues found that FUS sonication mainly modulated cell physical structure-related genes. ConclusionsThese feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.

"Invitae...announced enhanced chemistry of its Invitae Personalized Cancer Monitoring platform that helps detect circulating tumor DNA (ctDNA) as a biomarker for solid tumor malignancies. ctDNA can provide real-time insights on patient response or disease progression, support patient prognostic stratification and enable early detection of residual disease."

Further objectives are to correlate MRD status with pathologic complete response, determine the lead time to detection of recurrence compared to standard of care, and the association of MRD status with overall survival. Active enrollment started in March, 2022.

"Tecan has sued Invitae, ArcherDx, Integrated DNA Technologies, and Qiagen for allegedly infringing on patents related to nucleic acid enrichment and high-throughput sequencing methods...Tecan asserts in the first complaint that its technology underlies what Invitae, ArcherDx, and IDT refer to as their Anchored Multiplex PCR (AMP) target enrichment technology, which is found in Invitae's Personalized Cancer Monitoring (PCM) service and in ArcherDx's LiquidPlex, VariantPlex, and FusionPlex kits."

P=N/A; N=150; Recruiting; Sponsor:Invitae Corporation

The Invitae Personalized Cancer Monitoring assay, featuring a flexible patient-specific panel design with 18-50 variants, demonstrated high sensitivity and specificity for detecting ctDNA at variant allele frequencies as low as 0.008%. This assay may support patient prognostic stratification, provide real-time data on therapy responses, and enable early detection of residual/recurrent disease.

Two of the three patients with negative baseline MRD-HPV had detectable ctDNA within 1 month from the start of treatment. Conclusions The combination of PCM MRD and HPV ctDNA assays provide a highly sensitive approach for detection of low disease burden in early HPV-associated OPC patients.

Active enrollment started in March, 2022. Clinical trial information: NCT05219734.

"The research technology used in the study leverages a patient-specific panel developed to identify variants from a patient's own tumor rather than a static gene panel....In this publication, sensitivity and specificity of >99.9% was achieved at 0.008% variant allele frequency (AF) with 60ng cfDNA input and 0.03% variant AF with 10ng cfDNA input using a 50 variant patient-specific panel....Clinical specificity was assessed in 61 patients without evidence of disease in whom ctDNA was not expected to be detectable."

"Invitae...announced that its Personalized Cancer Monitoring (PCM™) assay, which helps detect minimal residual disease (MRD) in patients, has obtained its first commercial coverage in all solid tumors by Blue Shield of California. The policy, effective as of March 1, 2023, considers the test medically necessary for patients with stage I-IV cancer after surgical intervention for adjuvant or targeted therapy and/or monitoring for relapse or progression."

The use of the PCM assay, which featured ctDNA MRD testing utilizing patient-specific tumor mutation signatures, enabled sensitive detection of MRD in solid tumors with low DNA input. The PCM assay was able to detect the presence of MRD at low allelic fractions, which may enable early detection of MRD and patient relapse.

PCMTM detected breast cancer relapse with a long lead-time over clinical relapse, and strong association with relapse free survival, an advancement over previously published data with digital PCR MRD detection. Prospective, interventional trials are now required to assess whether treatment on the basis of MRD detection improves outcome, including the TRAK ER Trial (NCT04985266).

Standard endocrine therapy (GnRH analogues, aromatase inhibitors and tamoxifen) must have been received for a minimum of 6 months and a maximum of 7 years and be planned to continue for at least another 3 years. Secondary endpoints include relapse free interval, invasive disease free survival, distant recurrence free survival, overall survival and ctDNA clearance. (NCT04985266)

Methods Post-resection pre-treatment plasma from 1127 pts with stage IIIB-D/IV resected melanoma treated with nivolumab + ipilimumab vs nivolumab in the phase 3 CheckMate 915 study (NCT03068455) was retrospectively evaluated for ctDNA status and level, using a tumor-guided, pt-specific panel of up to 200 variants (Invitae Personalized Cancer MonitoringÔ). Table: 788O RFS probability by pre-treatment ctDNA status in CheckMate 915 treated patients conclusions Pre-treatment ctDNA was associated with increased risk of early recurrence across treatment arms. ctDNA is a useful biomarker for combined analyses predicting outcome for adjuvant melanoma.

"Invitae...announced full access to its Personalized Cancer Monitoring (PCM) platform to help detect minimal or molecular residual disease (MRD) in patients with solid tumors. Invitae PCM uses a novel set of personalized assays based on a patient's tumor to detect circulating tumor DNA (ctDNA) in blood, offering the ability to perform risk stratification, response assessment to treatment and detection of cancer recurrence, based on recent studies."