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Addressing One of the Most Common Dilemmas Faced by Oncologists

Cancer seen in the lungs of a human torso
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PD-1/PD-L1 immune checkpoint inhibitors have played a major role in revolutionizing cancer therapy. However, non-small cell lung cancer (NSCLC) patients fail to clinically benefit from antibodies targeting PD-1 and PD-L1 and, on average, only ~30% of patients will benefit from immunotherapy treatment.

Technology Networks spoke to Dr. Ofer Sharon, CEO of OncoHost, to learn more about the challenges in NSCLC treatment, how proteomics-based analysis could enable personalized cancer treatments and the advantages of a test to predict a patient’s clinical benefit from PD-1/PD-L1 inhibitors.

Kate Robinson (KR): Why is proteomics-based analysis important in personalized cancer treatment?

Ofer Sharon (OS): Proteomics-based analysis is crucial in personalized cancer treatment as it provides us with a holistic view of what is taking place inside the patient’s body. Proteins are the functional entities in the body and give us deep insight into the complex interplay between the patient, the tumor and the treatment, increasing the odds of identifying a clinically insightful biomarker.

However, proteins also pose a significant challenge in biomarker development. High variability of protein levels and expression between patients, overlap between different proteins and different biological processes and dynamic everchanging expression are only some of the issues associated.  To deal with so many features, complex interactions and dynamic modeling technologies are needed. Machine learning tools and pattern recognition capabilities combined with biology and bioinformatics are required to characterize such complex systems.

At OncoHost, we have developed a platform that combines these tools in order to develop a “hybrid” proteomic biomarker.

KR: How can biomarkers be used to guide NSCLC treatment decisions, and what challenges currently prevent this?

OS: The majority of NSCLC patients fail to benefit clinically from checkpoint inhibitors, notably antibodies targeting PD-1 and PD-L1, and uncertainties remain regarding how best to use these therapies in clinical practice. Response rates for metastatic NSCLC treated with immunotherapy still barely reach 30% – meaning that, on average, only about 3 of every 10 patients will benefit from treatment over time.

Given the risk of immune-related and other adverse effects associated with treatment, there has been a critical need to identify biomarkers that can accurately predict which patients will benefit and which will not.

With accurate biomarkers, clinicians can make informed decisions, identify resistance, intervene sooner, closely monitor patients with a high risk of resistance and choose next-line therapies based on patient and cancer biology, rather than relying on one-size-fits-all protocols.

The current PD-L1 biomarker has limited predictive value and does not direct physicians on whether they should treat the patient with immunotherapy or not, and in some cases, the guidelines are flexible, mostly due to the fact that we don’t know what the optimal choice for the patient is. For instance, if a patient has a PD-L1 >=50%, there is no guidance as to whether to administer monotherapy or combination therapy.

Physicians confront multiple predicaments occurring simultaneously when choosing a treatment plan for their lung cancer patients, finding themselves in a position of great uncertainty as they face a process with very limited support. With the current one-size-fits-all protocol, patients begin either targeted therapies or immunotherapy, alone or in combination with chemotherapy, and if both traditional and available biomarker-informed treatments fail, some patients are referred to clinical trials – as long as it isn’t too late.

A biomarker that goes beyond what PD-L1 offers is greatly needed. However, challenges persist in the widespread application of biomarker-guided treatments for NSCLC, including limited access to comprehensive biomarker testing, the heterogeneity of NSCLC tumors and the emergence of resistance mechanisms.

KR: How can the PROphet® test predict clinical benefit probability in response to PD-1/PD-L1 inhibitors

OS: The PROphet platform is a first-of-its-kind plasma-based proteomic pattern recognition tool that combines system biology, bioinformatics and machine learning to provide clinicians with actionable clinical insights, optimal therapy choices and a better understanding of their patients’ personalized cancer dynamics.

Our first test, PROphet NSCLC, identifies expression patterns in a panel of approximately 7,000 proteins using patient's blood. So, instead of measuring just one biomarker, we measure 7,000 potential biomarkers. As it is a very complex process to get a clear answer from such a high number of biomarkers, we looked for patterns in different cohorts from our clinical trial and identified various proteomic patterns for specific segments of patients.

The predictive power of those patterns – the outcome of differentially expressed proteins in individual patients – gave us a tool that is much more accurate than PD-L1 in terms of its ability to predict clinical benefit.

We can now provide real clinical utility for informing treatment decisions for NSCLC patients by adding resolution to the PD-L1 biomarker, enabling selection of the most suitable treatment modality for each patient.

Requiring just a single, pre-treatment blood sample, PROphet delivers a report that predicts a patient’s clinical benefit (progression-free survival>12 months) from PD-1/PD-L1 inhibitor immunotherapy-based treatment plans. Combining these findings with a patient’s PD-L1 level allows for a clear distinction between patients who will benefit from immunotherapy alone versus immunotherapy combined with chemotherapy. In addition, it may improve the patient’s overall response rate. PROphet thereby addresses one of the most common daily dilemmas of the oncologist with an accuracy and level of resolution that simply does not exist today.

With PROphet, physicians can offer the most effective plan for each individual patient, avoiding unnecessary treatments and their potential toxicities and enabling further refinement of current guidelines. We hope to create a shift in the industry and improve the lives of those fighting this disease.

KR: Were there any limitations of your study examining the analytical validity of the PROphet test?

OS: No clinical trial is perfect, and just like any scientific investigation, with new answers come new questions. Our trial demonstrated very strong predictive capabilities, but moving forward we plan to show that these predictions translate into measurable survival benefit.

In addition, while we clearly showed additional benefit over the existing biomarker, we would like to improve our “resolution” even further and identify even more subgroups of patients that may benefit from the personalized approach of PROphet.   

KR: Could the test be altered to guide the treatment of other cancers?

OS: Yes. The indication-agnostic nature of the PROphet platform allows for easy replicability across multiple indications and quick scale-up. Our pipeline includes melanoma, small cell lung cancer, renal cell carcinoma, head and neck cancer, urogenital cancer and more. We are also expanding the PROphet platform to cover more treatment modalities and at earlier disease stages i.e., targeted therapies, chemotherapy, radiation and combinations of these modalities.

In addition, the capabilities of PROphet extend beyond response prediction. They also include identifying resistance-associated proteins and related approved or investigational combination therapies that may benefit the individual patient. Watch this space!

KR: When did the test launch commercially?

OS: The PROphet NSCLC test launched commercially in the US in February 2023, and is sold as a Laboratory Developed Test (LDT) via our CLIA-certified lab in North Carolina. PROphet NSCLC is currently being utilized in ~50 cancer centers across the US.

PROphet is a prescription-only test and is billed to commercial plans. It can be ordered via our website.

Dr. Ofer Sharon was speaking to Kate Robinson, Assistant Editor for Technology Networks.

About the interviewee:

Dr. Ofer Sharon is the CEO of OncoHost.