Researchers are taking a new approach to sorting out why immunotherapy only works in select patients with hepatocellular carcinoma (HCC). A team of investigators is using newly developed high-throughput technologies to evaluate the therapeutic effects of the programmed death receptor 1 (PD-1) antibody (cemiplimab-rwlc), which was developed by Regeneron Pharmaceuticals, Inc, and Sanofi. It’s hoped this new investigation will help investigators gain insight into why so many patients still fail to respond to immunotherapy.1

“Our goal is to finally understand dynamic changes in the tumor immune microenvironment induced by novel immunotherapies and/or chemotherapy,” said study investigator Thomas Marron, MD, PhD, who is the assistant director of early-phase and immunotherapy trials at The Tisch Cancer Institute at Mount Sinai, New York, New York. 

He and his colleagues are conducting a phase 1 clinical trial to assess the clinical efficacy and response of patients to cemiplimab therapy in HCC, early-stage non-small cell lung cancer (NSCLC), and head and neck squamous cell carcinoma (HNSCC). The team will investigate single-cell mapping of cancer lesions and circulating immune cells, spatial mapping of the tumor tissues, and sequencing of the patient’s microbiome before and after treatment.

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What makes this investigation novel is that it attacks the problem with a multipronged approach and combines researchers with distinct expertise in medicine, immunology, technology, mathematics, and physics. Utilizing new proprietary technologies and platforms, the investigators hope to better characterize immune profiles and responses in a diverse range of disease settings. “We do not truly know how these agents work in vivo. So, we are not able to identify rational combinatorial approaches in surgical patients or metastatic patients,” Dr Marron told Cancer Therapy Advisor. “We need to identify biomarkers in order to identify who will benefit from therapy, so as to not waste our patients’ time, and cause unnecessary personal, physical, and financial toxicity.”

He said in the metastatic setting, some patients with HCC, NSCLC, or HNSCC have shown responses to immunotherapy. In NSCLC and HNSCC, the response rate to immunotherapy seems to increase when combined with chemotherapy, but still, half of patients do not respond. “Our goal is to use upfront immunotherapy to prime an immune response and decrease the chance of recurrence,” said Dr Marron. “We believe that [in] patients with locoregional disease, [and] with smaller, less heterogeneous tumors, there will likely be a higher response rate than seen in the metastatic setting.”