Physicians and Researchers Find EpiSwitch® CiRT Assay to be a Helpful Tool in Predicting Immunotherapy Response in Liver Cancer Patients

Last updated: 22 January 2025

Liver cancer, particularly unresectable hepatocellular carcinoma (uHCC), is the fourth leading cause of cancer-related death worldwide¹. 82% of liver cancer patients die within 5 years of being diagnosed with the disease². For patients facing advanced uHCC, the condition is rather dire, as treatment options are limited mainly to delaying disease progression rather than offering any hope of a cure. Patients diagnosed with stage 3 or 4 uHCC face average survival times of just 14 and 4 months, respectively.

Doctors aim to effectively choose the anticancer therapies that maximize efficacy while minimizing the risk of adverse effects associated with systemic treatment. There are three non-inferior uHCC regimens, including immuno-oncology (IO) and non-IO options. Lenvatinib, a non-IO tyrosine kinase inhibitor (TKI), blocks the pathways involved in tumor growth and blood vessel formation to cause cancer regression². The IO options include immune checkpoint inhibitor (ICI) therapies, such as Atezolizumab + Bevacizumab (commonly known as AtezoBev) and Durvalumab + Tremelimumab (widely known as STRIDE). ICIs contain antibodies that bind to programmed-cell death proteins to enhance the immune system's ability to target and eliminate the primary tumor and metastatic deposits as well⁴.

AtezoBev is the primary standard treatment, with Atezolizumab (a PD-L1 inhibitor) enhancing the immune system's ability to attack cancer cells, while Bevacizumab (an anti-VEGF agent) inhibits blood vessel growth. In cases where the patient experiences bleeding complications, IO treatment may be adjusted to STRIDE, which includes Durvalumab (PD-1 inhibitor) and Tremelimumab (CTLA-4 inhibitor) to boost the immune response against tumors. Currently, these treatments for uHCC are administered without the guidance of reliable molecular biomarkers, meaning patients receive these drugs without knowing whether they are likely to respond⁵. As a result, optimizing first-line treatment is crucial, as nearly 50% of patients with uHCC do not make it to second-line therapy.

The EpiSwitch® CiRT (Checkpoint inhibitor Response Test) transforms the liver cancer treatment landscape by using epigenetic molecular biomarkers located in immune cells to assess each patient's unique profile. It is a simple blood test yet a powerful tool to guide doctors in selecting the most effective therapy based on their patients' likelihood of response to different treatment options with best-in-class accuracy. CiRT provides a binary high-probability (HP) or low-probability (LP) score for immunotherapy response from a small blood draw. By grouping patients into HP or LP cohorts, CiRT allows a more personalized approach, pinpointing those more likely to benefit from immunotherapy. Those with the molecular profile associated with a low probability of response to ICIs can then be placed on an alternative anticancer modality (e.g., targeted therapies like Lenvatinib).

Doctors are relying on EpiSwitch® CiRT to determine their treatment decisions between IO and non-IO regimens for patients with uHCC. Strikingly, these options have been deemed non-inferior to each other in terms of length of survival. For those classified as low-probability (LP) responders to immunotherapy by CiRT, the recommended treatment option is a non-inferior TKI (lenvatinib). On the other hand, patients with high-probability (HP) results can significantly benefit from immunotherapy options like Atezolizumab + Bevacizumab (AtezoBev) and/or Durvalumab + Tremelimumab (STRIDE), as they are more likely to have positive responses and longer progression-free survival (PFS). This allows doctors to prioritize immunotherapy for patients with HP profiles while exploring alternative yet targeted treatment options for those with LP scores, minimizing unnecessary exposure to ineffective drugs.

Oxford BioDynamics and Georgetown University Medical Center collaborated on a study and prepared a data package for the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium. The abstract was recently accepted for presentation in San Francisco in January 2025. This presentation will highlight CiRT's accuracy in predicting immunotherapy responses in liver and gastrointestinal cancers, drawing from clinical data involving liver cancer patients treated in their system. The study reveals how EpiSwitch® CiRT identifies patients likely to achieve longer progression-free survival (PFS) in uHCC and GI tumors.

While various non-inferior treatment options for uHCC exist, selecting the most suitable regimen remains a significant challenge for physicians and patients. However, innovative technologies like EpiSwitch® CiRT offer a promising solution. By accurately predicting a patient's likelihood of responding to immunotherapy, CiRT is helping to reshape patient care, improving survival outcomes, and enhancing the quality of life for liver cancer patients facing difficult treatment decisions.

About the Authors: Thao Nguyen is a graduate student at Georgetown University Medical Center and Dr. Ryan Mathis is a medical doctor who graduated from Penn State School of Medicine and serves as the Company's Vice President of Market Access and principal investigator of the PROWES study assessing CiRT's real-world clinical utility and socio-economic benefit.

References

1) Oh, JH., & Jun, D. W. (2023). The latest global burden of liver cancer: A past and present threat. Clinical and Molecular Hepatology, 29(2), 355–357. https://doi.org/10.3350/cmh.2023.0070

2) Leowattana, W., Leowattana, T., & Leowattana, P. (2023). Systemic treatment for unresectable hepatocellular carcinoma. World Journal of Gastroenterology, 29(10), 1551–1568. https://doi.org/10.3748/wjg.v29.i10.1551

3) Tsoris, A., & Marlar, C. A. (2023). Use of the Child Pugh score in liver disease. StatPearls Publishing. https://pubmed.ncbi.nlm.nih.gov/31194448/

4) Shiravand, Y., Khodadadi, F., Kashani, S. M. A., et al. (2022). Immune checkpoint inhibitors in cancer therapy. Current Oncology, 29(5), 3044–3060. https://doi.org/10.3390/curroncol29050247

5) Yang, F., Wang, J. F., Wang, Y., Liu, B., & Molina, J. R. (2021). Comparative analysis of predictive biomarkers for PD-1/PD-L1 inhibitors in cancers: Developments and challenges. Cancers (Basel), 14(1), 109. https://doi.org/10.3390/cancers14010109

6) He, RA., Ouf, M., Aggarwal, N., Lee, J., Wang, HK., Sadagopan, N., Mathis, R., Abdo, J.. Evaluation of EpiSwitch in Predicting Immunotherapy Response in Hepatocellular Carcinoma and Gastrointestinal Tumors. Journal of Clinical Oncology. Abstract under review as of Oct-2025.