Weekly Liquid Biopsy Insights

(9/17/2020) Epic Sciences and MSK find a potential prognostic marker for mCRPC

Epic Sciences and researchers from MSK identified that a chromosomal instability marker on circulating tumor cells found in metastatic prostate cancer may have prognostic value and could be used to guide therapeutic decisions. The researchers found that the number of large scale transitions (LSTs) found in CTCs was associated with poor outcomes and developed an algorithm that can analyze CTC images captured as a result of Epic’s immunofluorescent staining platform. In a prospective study using samples from 294 patients (10,240 CTCs) a cutoff of 9 or more LSTs in a single CTC had a clinical sensitivity 68% and 84% specificity of predicting worse overall survival.

Other news includes the 9% stock drop Illumina saw after rumors of a potential acquisition of Grail (which came shortly after Grails IPO announcement) and Natera’s plan to look for a combined value for their Prospera and Signatera assay for oncology treatment decisions.

Recent Headlines

Market Highlights

Natera Launches Proposed Follow-On Offering | Sep 9, 2020
Streck Cell-Free DNA BCT® receives U.S. FDA De Novo clearance | Sep 11, 2020
Genetron develops testing kit for China’s nationwide cancer screening program | Sep 14, 2020
Natera Launches Initiative to Transform the Management of Cancer Patients in Organ Transplantation | Sep 14, 2020
Canexia Health Closes New Financing Round to Accelerate Precision Oncology Roadmap | Sep 16, 2020
Illumina’s Stock Falls 9 Percent on Grail Acquisition Rumors | Sep 16, 2020

Research Highlights

Epic Sciences, MSK Identify Potential Prostate Cancer Therapy Response Biomarker | Sep 10, 2020
Helio Health Announces Collaboration with Top National Cancer Centers | Sep 10, 2020

(9/10/20) FoundationOne Liquid CDx approval; Sysmex Inostics publishes on value of OncoBEAM in mPDAC

Liquid biopsies are pushing further into routine clinical care by receiving favorable approval/ coverage decisions by regulatory/ reimbursement bodies. In late August, Foundation Medicine’s liquid assay was approved as a CDx for Rubraca (a PARP inhibitor for prostate cancer) and three TKI’s for NSCLC treatment. The company intends to leverage the broad range of targets of FoundationOne Liquid CDx (a comprehensive genomic profiling assay) to pursue additional CDx claims. A potential expansion would be to seek CDx status for BluePrint’s and Genetech’s Gavreto, which received accelerated approval for metastatic NSCLC patients harboring RET fusions. Guardant and FMI can both detect RET fusions however only Thermo’s Oncomine tissue test is the only approved CDx platform for RET fusions. Additionally, Natera received a final local coverage decision of Signatera for serial monitoring of MRD in stage II / III CRC patients from CMS. This final local coverage decision is in line with the draft decision that was issued in Aug of 2019.

In other news, Sysmex Inostics announced a publication highlighting the potential value of their digital PCR assay, OncoBEAM RAS for metastatic pancreatic ductal adenocarcinoma. The study showed that levels of circulating RAS mutations may be an improved biomarker to CA19-9 (a non-tumor specific protein biomarker) for prognostic evaluation and real-time tumor response monitoring. This assay could add to the information on hand when oncologists are making clinical decisions, which is key when treating such an aggressive cancer.

Recent Headlines

Market Highlights

Research Highlights

(8/5/2020) Singlera narrows focus to CRC; miR Scientific named as Fierce Innovation Finalist; More news on ArcherDx, Natera and Personalis

While Singlera’s 10 yr. retrospective study generated positive data for PanSeer (4 cancers) the company has decided to narrow its near-mid term commercialization efforts on colorectal cancer with an assay named ColonES. Reducing the scope to one cancer with clear screening guidelines and proven efficacy of assays for detection instead of imaging (e.g., ultrasound, MRI etc.) should lighten the lift required for Singlera to prove clinical utility and gain reimbursement. This path was forged by Exact Sciences but is crowded by the likes of Freenome and Guardant who are in hopeful pursuit. The pivotal study for ColonES is expected to launch in later 2020.

Another indication with an approved blood test to aid in cancer detection is prostate cancer. However, it is no secret that there needs to be a better tool than PSA for detecting high-grade prostate cancer. This week, miR Scientific was selected as a finalist for the 2020 Life Sciences Fierce Innovation Awards. miR’s Sentinal Prostate Test detects small-non-coding RNAs from a urinary exosomes to detect cancer as well as clasify the risk category of the cancer. The assay’s validation data revealed that Sentinal detects cancer with 94% sensitivity / 92% specificity, and correctly categorizes Gleason Grade (GG) 1 from GG 2 – 4 with 93% sensitivity / 90% specificity, as well as GG 1 – 2 from GG 3 – 5 with 94% sensitivity / 96% specificity. Correct categorization of a patients risk can save them from unnecessary and risky prostate biopsies.

Additionally, Natera, Personalis, and ArcherDx had stories this week. Be sure to take a look at them in the links below!

Recent Headlines

Market Highlights

Research Highlights

New Prostate Test Could Help African American Men | Jul 29, 2020
Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity | July 29, 2020
Efficient mutation screening for cervical cancers from circulating tumor dna in blood | Jul 29, 2020
Two thirds of lung cancers detected at early stage using blood test and CT scans | Jul 31, 2020
Patient specific circulating tumor DNA fingerprints to monitor treatment response across multiple tumors | Aug 1, 2020

(7/28/20) - Singlera releases preliminary PanSeer Data, suggesting a 4 year lead time; Methylation markers may help predict CPI Tx response

The largest buzz in headlines this week was generated by Singlera when they released positive preliminary data from the Taizhou Longitudinal (TZL) Study for PanSeer. PanSeer uses ctDNA methylation markers to detect stomach, esophageal, colorectal, lung or liver cancers and will compete with the likes of Thrive Earlier Detection (~10 cancers) and GRAIL (>50 cancers) as a blood-based pan-cancer screening assay. The TZL study collected samples from 123,115 healthy patients over time while they were monitored for cancer occurrence. The preliminary analysis consisted of a group of 605 asymptomatic patients, 191 of whom developed one of the 5 cancers measured by PanSeer. It was found that PanSeer detected cancer in 88% of these patients post-diagnosis at 96% specificity. PanSeer was able to identify 95% of asymptomatic individuals who were later diagnosed with cancer within 4 years of their blood draw. Further validation is needed, but the prospects of identifying cancer 4 years prior to conventional diagnosis is certainly exciting.

ctDNA methylation has established itself as a crucial analyte for the early detection of cancer and may prove to be useful later in cancer care. Genome Profiling and Fox Chase Cancer Center are collaborating to develop a potential predictive marker for checkpoint inhibitors in lung cancer patients. Immuno-oncology is known to only have drastic results in a limited group of patients. Markers like PD-L1 status and Tumor Mutation Burden are still being understood and are primarily determined by a tissue sample. The goal of this collaboration is to determine if methylation sites on circulating immune cells can predict a lung cancer patient’s response to CPIs. If successful, this test could save a patient from undergoing a risky biopsy as well as better inform treatment decisions.

Recent Headlines

Market Highlights

Research Highlights

(7/21/20) - AnchorDx collaborating with J&J; Canadian consortium led by Canexia Health to improve targeted cancer treatment

AnchorDx is launching a clinical study through their partnership with Johnson &m Johnson. The study will enroll 3000 patients with lung nodules identified by a CT scan and will be used to determine if Anchor’s ~$100 methylation based blood test has clinical utility in detecting lung cancer early by differentiating benign nodules from malignant nodules.

Angle announced that Parsortix, a CTC capture device, identified targetable mutations in metastatic breast cancer that were missed in single site biopsies. The company plans to file their FDA submission for Parsortix in Q3 2020. This announcement comes amidst other research movements for liquid biopsy in breast cancer, which is exciting since this cancer is known to be low shedding and difficult to develop assays for.

Canexia Health (formerly Contextual Genomics) is leading a consortium whose initiative is to improve testing and treatment of Canadian cancer patients during this pandemic. The project is called ACTT (Access to Cancer Testing and Treatment) and will offer Canexia’s liquid biopsy test (Follow It) to recurrent or metastatic lung, breast, or colon cancer. Many patients have forgone genomic profiling during the corona pandemic out of fear of contraction. Other patients are facing long wait times to get surgery due to hospital congestion and may not be able to have a tissue biopsy collected. Time is critical in cancer care and having access to targeted therapies could improve patient outcomes. The consortium is using LBx to help alleviate the complications caused by the pandemic and could have long lasting impacts on cancer care.

Recent Headlines

Market Highlights

Research Highlights

Presence of cfDNA, CTCs Predicts Recurrence in Triple-Negative Breast Cancer | July 10, 2020
The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast—Long-Term Prognostic Significance | July 17, 2020 (PDF download)

(7/10/20) - AnchorDx presents positive data for $100 methylation assay; Natera releases data at ESMO GI; Guardant to develop CDx for Janssen

AnchorDX presented early results for their Aurora early cancer detection assay at AACR last week. Aurora uses 100 – 200 methylation markers to detect 6 common cancer types (lung, breast, colorectal, esophagus, and liver) and was created using both TCGA and Anchor’s in-house database of 2,000 tissue and 4,000 plasma samples. Anchor’s in-house data is skewed towards early cancer patients, which they claim helped their test achieve superior sensitivity and specificity compared to other early detection assays. Aurora was tested using 246 lung, breast and colorectal cancer patient samples, and 141 normal controls. At a pre-specified specificity of 99% the test showed 82%, 63%, and 55% sensitivity in Stage 1 lung, breast, and colorectal cancers, respectively. On top of this impressive performance, the company, and wisely so, is targeting a price point of ~$100 which is expected to increase access if Aurora can continue proving clinical utility. Other companies targeting early detection assays have amassed higher levels of clinical data on their road to commercialization, so it will be interesting to see how Anchor’s data holds in a larger prospective dataset.

Natera announced further evidence of it’s Singatera platform at ESMO GI 2020. The studies showed that Signatera was able to detect 100% of oligometastatic patient’s pre-surgery, as well as highlighted the study design for a prospective and observational trial (GALAXY) which is part of the CIRCULATE-Japan trial. CIRCULATE-JAPAN is aimed at optimizing ctDNA guided treatment strategies in Stage II-III CRC patients. In a press release, Natera’s Senior Medical Director of Oncology claimed that “Now that Signatura is being used in prospective interventional trials, we’re seeing confirmation that it can help inform treatment decisions after oligometastatic resection in the 20 percent to 30 percent of patients with metastatic CRC,”.

In an interesting analysis of reimbursement coverage of liquid biopsies it was found that the ~40% of payers offer some coverage of ctDNA panels as of mid -2019 – a sharp increase from 0% in 2016. Coverage also expanded from just NSCLC to 12 cancers as well as from single-gene tests to 73 gene tests. A limitation of coverage for monitoring assays was noted, with only 11% of payers having positive claims towards ctDNA for monitoring purposes.

Recent Headlines

Market Highlights

Research Highlights

Study Supports Using Comprehensive ctDNA Testing in Patients with NSCLC | Jul 3, 2020
Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention | Jul 3, 2020

(7/1/20) - Guardant launches clinico-genomic platform GuardantINFORM, Inivata showcases RaDaR monitoring studies at AACR

Guardant has launched the GuardantINFORM platform, a dataset that combines de-identified longitudinal clinical information and genomic data collected from the Guardant360 liquid biopsy test. Notable applications for the platforms include targeted drug development, clinical trial optimization, and post-marketing studies. As the market leader in liquid biopsy testing, the size of Guardant’s dataset is impressive, with samples from over 100,000 patients have been accumulated over the past 5 years, according to Helmy Eltoukhy, Guardant Health co-founder and CEO. Across the industry, there is significant appetite for real-world evidence and clinico-genomics data to inform research and product development (note the Roche Group’s Prospective Clinical-Genomic study launched a month ago), and we are just starting to leverage its potential.
At the AACR meeting last week, Inivata and collaborators at the Cancer Research UK Cambridge Institute presented results from two studies using the RaDaR ctDNA monitoring assay. As part of one study regarding the analytical development, the RaDaR assay was used against a variety of cancer cell lines, DNA reference material, and tissue samples to assess performance at various dilutions. Tracking 48 mutations, the RaDaR assay demonstrated 97% sensitivity using 20,000 copies, and 63% sensitivity using 4,000 copies of DNA input.

In a separate study focused on early stage NSCLC, 90 patients were recruited from the LUng Cancer CIrculating Tumour DNA (LUCID) Study and monitored post-surgical resection and every 3 months for 9 months. ctDNA was identified in 35% of baseline samples from stage I patients, and >90% of samples from stage II and stage III patients, and the results suggest that that RaDaR could identify ctDNA 6-12 months ahead of typical disease progression in 60% of patients.

The RaDaR assay partitions the sample before sequencing, presumably increasing the signal-to-noise ratio to detect low-frequency variants prior to sequencing. Combined with the approach of using a personalized, mid-sized NGS panel, RaDaR could prove to be strong competition against other companies in the monitoring market (including Natera, Guardant, and ArcherDX).

Recent Headlines

Market Highlights

Biocept reaches deal to cover out-of-network patients for its liquid biopsy tests | June 24, 2020
Guardant Health Launches Real-World Clinical-Genomic Platform to Accelerate Precision Oncology Drug Development | June 23, 2020
Inivata Demonstrates Potential of ctDNA Assay for Cancer Recurrence, MRD Applications | June 25, 2020
NeoGenomics Launches Comprehensive Suite of Solid Tumor Liquid Biopsy Tests for Cancer Patients | June 29, 2020

Research Highlights