NEW YORK – OncoHost has identified a protein signature using its plasma-based immunoarray platform Prophet that may identify which advanced non-small cell lung cancer patients will respond to immunotherapy.
In data from the ongoing, observational Prophetic study presented at the European Society for Medical Oncology Congress, researchers identified a set of eight proteins and two clinical parameters that appeared to differentiate NSCLC patients who are likely to respond to immune checkpoint inhibitors from those who aren't.
The Prophetic trial is a multicohort study sponsored by OncoHost that is exploring predictive algorithms that can better characterize lung and melanoma cancer patients' responses to various anti-cancer therapies. At the ESMO Congress, the company reported data specifically from 108 advanced NSCLC patients who had received immunotherapy. Of those, 80 patients had responded to treatment, while 28 had not.
To conduct the analysis, researchers obtained plasma samples from NSCLC patients at baseline and early in their treatment course, as well as clinical data. They then profiled about 1,000 proteins using an assay from OncoHost and applied machine learning algorithms to stratify responders and non-responders on a training cohort of 78 patients.
They identified a predictive signature comprising eight proteins and two clinical parameters, which they further validated in a cohort of 30 patients, yielding a specificity of 0.81 and a negative predictive value of 0.77. The researchers conducted further bioinformatics analysis to identify specific biological features distinguishing responders and non-responders.
"[We're] trying to use a protein signature — protein changes in the plasma following treatment — in order to characterize the interaction between the patient, tumor, and the therapy," said OncoHost CEO Ofer Sharon. "This is the triangle that OncoHost is operating in."
Although Sharon declined to disclose the proteins and clinical parameters comprising the signature, he mentioned that the differences between responders and non-responders in the latest analysis suggested the involvement of therapy-specific resistance mechanisms.
The Prophet platform uses immunoarrays to analyze roughly 1,000 proteins through a combination of immunoassay-based biochemistry and machine learning. The proteins analyzed in the array come from the research of Yuval Shaked, a researcher at the Israel Institute of Technology and OncoHost's chief scientific adviser and cofounder.
Although cancer treatment often focuses on killing or neutralizing tumors, patients' bodies can produce factors such as signaling molecules, growth factors, and enzymes that can promote tumor growth or therapy resistance. Characterizing the role of these other factors, in addition to parsing the biological features of the tumor, can provide insights into the likelihood that a patient will respond to immunotherapy, and may even reveal other druggable targets in non-responders.
Since fewer than 20 percent of patients are estimated to respond to immune checkpoint inhibitor therapy, and existing biomarkers using PD-L1 expression or tumor mutational burden aren't optimal, there is currently a need for better approaches to identifying responders and non-responders. Researchers are increasingly exploring tumor-centric treatment strategies alongside methods to regulate host response.
Sharon anticipates that combining the Prophet platform with tests measuring tumor biomarkers will provide a more granular picture of the resistance mechanisms at play in patients who don't respond to checkpoint inhibitors. "This is exactly the approach we want to take," Sharon said. "We are going to take this multiomics approach and we are going to add related factors … like cell-free DNA and circulating tumor DNA."
According to Sharon, OncoHost has two collaborations in the works to explore this, although he couldn't yet say with whom as the agreements are not finalized.
Federico Giorgi, a professor of pharmacy and biotechnology at the University of Bologna in Italy whose past research has involved systems biology approaches to overcoming cancer drug resistance, expressed optimism regarding the Prophetic trial results and agreed with Sharon about the need for a multiomics approach. Giorgi, who isn't involved in Prophetic, also cautioned that plasma-based results should still be corroborated by other methods.
"While plasma samples are more easily accessible," he said, "they must be functionally complemented by biopsies, at least in patients, because we need to know if the differences between cancer [patients] and normal [controls] in their plasma reflect actual differences in the tumor." The insights from such an approach can elucidate the biological mechanisms that may be exploited by checkpoint inhibitors in combination with other drugs to make non-responders into responders, but he added that this "cannot be inferred from plasma proteomics alone."
While the Prophet assay results have not yet been compared to tissue biopsy data, OncoHost plans to explore that relationship in an upcoming collaborative trial.
Meanwhile, slightly more than 600 lung cancer (NSCLC or small-cell lung cancer) and melanoma patients are currently enrolled in the Prophetic study, out of an estimated total enrollment of 2,000 patients. At the American Society of Clinical Oncology's annual meeting last year, OncoHost reported on the performance of a 10-protein melanoma signature using data from 34 melanoma patients in that study.
OncoHost hopes to launch its assays first as laboratory-developed tests early next year, starting with the lung cancer assay, and subsequently plans to seek regulatory approval from the US Food and Drug Administration.
The company raised $8 million in Series B funding at the beginning of the year, part of which financed the opening of a US-based affiliate. OncoHost intends to open a physical lab either later this year or early next year in support of launching Prophet commercially in the US, followed by Europe.
Initially, OncoHost expects to accept patients' plasma samples from clinics and analyze them in its lab. In the future, the company also has ambitions to develop bedside products.
While OncoHost plans to remain a diagnostic company, its technology can facilitate research into combination therapies and drug repositioning, areas in which Sharon expects the firm to have a presence through future collaborations.
"Since we are discovering very interesting insights into tumor and host biology and finding proteins that are targetable, one of the objectives of the company is to develop collaborations with pharmaceutical partners [for] specific targets [of] combinations of drugs," he said.