NEW YORK (GenomeWeb) – With its first commercial diagnostic now fully launched and awaiting a final coverage decision by Medicare, Epic Sciences is keeping quiet about concrete plans for a pipeline of additional clinical assays, though it continues to collect data from research studies which may provide possibilities for future translation.
One interesting new application was hinted at in a pharmaceutical study published in JAMA Oncology earlier this summer. Investigators applied Epic's cell-analysis technology to blood samples from metastatic prostate cancer patients treated with Bind Therapeutics' investigational BIND-014, an anti-PSMA antibody-drug conjugate (ADC).
According to the authors, the presence of PSMA-positive circulating tumor cells (CTCs) was strongly associated with therapeutic response and clinical outcomes to treatment in the cohort.
Epic announced last month that it had completed a $52 million Series E financing, which would support the advancement of a portfolio of new predictive tests and decision support tools for precision medicine. Ryan Dittamore, the firm's chief of medical innovation, said that the company could not discuss whether it might use its platform for identifying responsive patients in the clinic — as a companion diagnostic — for either this drug, or the multiple other similar ADCs being investigated.
But he highlighted the results as evidence of what a technology like Epic's can provide both for the early development of this class of drugs — as a way to understand if and why therapies might be working or not working — and potentially as a diagnostic, to identify those who are more likely to benefit based on the presence or absence of a drug's target in their tumor cells.
Other recent data that Epic has made public have involved the ability of its platform to assess the overall heterogeneity of circulating tumor cells, using a measure of how diverse the population of cancer cells is to predict whether a patient is likely to respond better to standard chemotherapy or to genetically targeted treatment.
The company is also increasingly applying its technology to investigate how combined analyses of tumor cells in the blood and human immune cells can be useful in immunotherapy drug development and, hopefully, in companion diagnostic applications for specific immunooncology drugs.
According to Dittamore, the recent PSMA study with Bind illustrates how applying Epic's platform in the earlier stages of drug development can translate to utility for patient selection in later trials, and potentially, to companion diagnostic development. He also noted that the company is now working with at least 65 pharmaceutical companies.
Investigators studying the Bind PSMA-targeted chemo conjugate were using the platform to explore patient response retrospectively: looking at which patients had tumor cells in their blood that expressed PSMA on their outer membranes and then checking to see if those cells were reduced after treatment. But the same platform also allowed them to compare patients with and without the biomarker-positive cells, exploring whether that corresponded to their outcomes.
According to the authors, 16 of 18 patients in the phase II trial had CTCs present at baseline and 11 had CTCs with PSMA expression above a set analytical threshold level. But overall, PSMA expression was heterogeneous — every patient who had PSMA-positive CTCs also had populations of PSMA-negative CTCs.
Patients who had PSMA-positive CTCs were more responsive to the treatment than those who did not, suggesting that measuring PSMA expression could help identify responsive patients ahead of time in future trials, and possibly, if further validated, offer a way to guide therapy for patients in the clinic.
Immunotherapy
In addition to the ability to detect specific molecular markers on circulating tumor cells, as in the PSMA experiments, Epic's platform, which arrays the full cohort of non-blood cells for imaging-based analysis and downstream genomics, can in parallel analyze phenotypic or morphologic cellular heterogeneity, perform a molecular readout on CTCs, and assay the body's immune cells also present in these samples.
Dittamore added that the analysis of immune cells is something the company is increasingly investigating with pharmaceutical partners. "We have created specific panels for T cell activation, and we are working on T cell exhaustion now," he said.
At the International Cancer Immunotherapy Conference this week in New York, multiple presenters highlighted how research is increasingly demonstrating that both tumor immunogenicity and the body's response to that prompt are factors in the fight against cancer, and in the success or failure of immunooncology drugs.
Having a readout on both of those questions — whether the tumor is immunogenic, and whether there is a robust immune response taking place — may be crucial in the future in making decisions about how to treat patients, Dittamore argued. For example, the first case might prompt adding vaccines or radiation to potentially make tumors more recognizable to the immune system. In the latter, clinicians would need to address the inability of immune cells to mount a response to a tumor they can already recognize.
In terms of the first question — whether tumors are making themselves known to the immune system — Epic announced last year that it is providing specific tools to measure microsatellite instability (MSI) and chromosomal instability in CTCs. In an email at the time, Dittamore said that an example of an application might be in trying to see if CTC clonality, or heterogeneity, might help explain why only some of the patients who respond to immunotherapies test positive for MSI using tumor tissue tests.
Heterogeneity
The company also continues to explore blood-based detection of tumor heterogeneity as a possible tool for guiding decisions about whether patients might be best served by standard chemotherapy over genetically or hormonally targeted drugs.
The company has shared data from studies of this in prostate cancer, and at this summer's American Society for Clinical Oncology annual meeting it presented data from efforts to try to recapitulate this in breast cancer.
"Based on what we see in our studies, there are very few patients with advanced cancer who are clonally homogeneous, so it makes sense that with targeted agents you might kill off one of four or five subspecies, but that might not make a difference," Dittamore said.
The result, he argued, is that a large number of patients in the metastatic space just won't respond to targeted therapies, but are still getting broad genomic sequencing and being tried on these drugs based on mutations detected.
"You could potentially see [CTC heterogeneity] being a pre-screen for who should get sequencing and targeted therapy … but we are early in this and it would be a lot of work to demonstrate that indication by indication," he said.