Liquid Biopsy Trends to Watch at ASCO 2018
Guardant leads, Grail makes strides with CCGA, and more
Over 39,000 attendees are expected to descend upon McCormick Place in just one short week. The theme for this year’s conference, “Expanding the Reach of Precision Medicine” will focus on expanding access to new discoveries so that every cancer patient will have the opportunity to benefit from advances in precision medicine.
Over 5,000 ASCO abstracts have already been released so far, with some expected to be released at the time of presentation. DeciBio ingested the released abstracts here, tagging any that mention one of three major liquid biopsy biomarkers (circulating nucleic acids DNA/RNA, circulating tumor cells and exosomes). By our classification, there were nearly 500 liquid biopsy abstracts.
With ASCO now only a week away, here are five highlights from the abstracts worth taking note of:
Guardant soars in liquid biopsy
Perhaps unsurprisingly, Guardant Health takes the lead at ASCO 2018 with 23 liquid biopsy abstracts (Guardant’s other two abstracts this year include a cohort study and RET fusions, both focused on NSCLC patients).
As far as notable results, one of Guardant’s studies found that both cancer type (lung vs. breast) and physician type (AMC-based providers vs. community practitioners) have a significant impact on use of test results. For the former, actionable results result in a management change for lung cancer 63% of the time vs. only 28% in breast. For the latter, results of cfDNA tests lead to action more often with community providers than AMC-based providers (61% vs. 31%). In another, more bioinformatics-focused study, Guardant found that recurrence prediction is improved by filtering using a variant classifier without prior knowledge of tumor genotype, thereby enhancing clinical feasibility of ctDNA diagnostics for decision making in early-stage disease.
In terms of authorship, Guardant continues to collaborate with the usual suspects: NCCNs like MD Anderson and Memorial Sloan Kettering (who sit at the core of liquid biopsy research networks), integrated delivery networks like Dignity Health, as well as major comprehensive cancer centers like Sylvester Comprehensive Cancer Center and the Moffitt Cancer Center. While some people have indicated that Guardant may have less presence ex-U.S., we did notice Guardant seems to be at least co-publishing with several European and LATAM-based institutions, such as Niguarda Cancer Center (Milan), Hospital Universitario de la Princesa (Madrid), Oncosalud-AUNA (Lima), and Biotecgen (Bogota). Given the number of Chinese authors, there was a notable lack of APAC representation among Guardant’s authored abstracts. Guardant did co-author one study with Seoul National University Hospital and the National Cancer Center in Singapore. However, this abstract only used G360 to evaluate clinical endpoints in measuring therapeutic outcomes of a novel monoclonal antibody.
Chinese researchers flood the liquid biopsy research landscape
While Chinese researchers authored ~10% of total abstracts, they comprised nearly ~20% of liquid biopsy-related abstracts (i.e., those related to circulating nucleic acids, circulating tumor cells, or exosomes) at ASCO 2018. Within academia, the Chinese Academy of Medical Sciences, Peking University (“BeiDa”), and the Chinese University of Hong Kong were most ubiquitous; within industry, HaploX Biotechnology published three abstracts related to early detection and monitoring using its ctDNA test, while CellMax Life published three studies related to treatment selection and early detection using its CTC test.
Finally, Predicine*, which launched PredicineATLAS, a 600-gene ctDNA+ ctRNA panel for treatment and disease monitoring at AACR this year, published a study showing 100% specificity and 91% accuracy in predicting HER2 amplification status for pre-treatment baseline samples in Chinese metastatic breast cancer.
Grail continues to make strides with CCGA
Following Grail’s announcement of its oversubscribed $300M Series C financing (led by Ally Bridge Group), we are looking forward to latest updates from the CCGA and STRIVE studies, including further details on the accuracy of Grail’s classifier algorithm. Despite skepticism expressed by attendees at AACR and at-large, Grail states they are on schedule for the launch of their first early detection assay (for nasopharyngeal cancer) in Hong Kong later this year.
All four of their abstracts (one of which will be released Saturday, June 2) are based on results from the CCGA study (NCT02889978), with a primary focus on validating their ultra-sensitive sequencing assay. One of their more exploratory studies demonstrates that clonal hematopoiesis of indeterminate potential (CHIP) signalling, which is reported to occur in up to 30% of individuals 60-70 years of age, may be much more common than previously thought. CHIP is a risk factor for hematologic malignancies and cardiovascular disease, with implications for the interpretation of cfDNA variants. The researchers of this study conclude that the clinical significance of CHIP must be accounted for when interpreting cfDNA variants for both early cancer detection and tumor genotyping (liquid biopsy).
Nant picks up steam
Despite recent layoffs, NantOmics and NantHealth, two of the nine members of the NantWorks ecosystem, published three liquid biopsy abstracts (of their total 18). These abstracts focus on gene expression of cfRNA, RNA-seq analyses, and cfRNA plasma monitoring. Notable results from their clinical trial (NCT02853097) showed significant differences in cfRNA levels between cancer patients and healthy individuals, indicating total cfRNA level itself may be effective as a biomarker for presence of cancer and/or for recurrence monitoring.
In addition, Nant will unveil their new 26-analyte cfDNA/cfRNA tests focused on monitoring response to I/O therapies including Keytruda, Opdivo, and Xtandi. Stay tuned for our post-ASCO analysis on Nant’s liquid biopsy test.
Novel biomarkers and technological approaches in liquid biopsy
GeneSeeq, a Toronto-based company with Chinese headquarters in Nanjing, found a distinct CSF exosomal microRNA signature, which may indicate progression of leptomeningeal metastasis (LM), a serious complication in NSCLC patients. Their NGS-based 416-gene panel requires only 8ml of blood and claims 100% coverage of all exons as well as fusions, indels and amplifications.
With regards to new technological approaches in liquid biopsy, researchers in Israel and Spain captured bone marrow and circulating plasma cells using single cell RNA-sequencing (scRNA-seq), identifying new pathways and potential targets in multiple myeloma. On the other side of the globe, researchers from Kitakyushu, Japan, have developed a novel CTC-chip showing superior efficiency and performance in detection of CTCs over CellSearch, which continues to be the only clinically approved platform to detect CTCs. Their novel platform may be useful in evaluation of tumor progression and in prediction of prognosis in malignant pleural mesothelioma (MPM).
Underrepresentation from Illumina, Foundation Medicine, Tempus Labs and Freenome
A few key players are missing from the liquid biopsy abstract pool this year. Most notably, Illumina has no publications (they at least had one in 2017 and two in 2016), Foundation Medicine has two related to liquid biopsy (of their total 42), Tempus has one (total) and Freenome, who had two posters at AACR this year, has none. Nonetheless, we will be on the lookout for key updates from these liquid biopsy players at ASCO this year.
* Note: While Predicine operates in Shanghai, China, the company is headquartered in California.