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. Its 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 understanddynamic changes in the tumor immune microenvironment induced by novelimmunotherapies and/or chemotherapy, said study investigator Thomas Marron,MD, PhD, who is the assistant director of early-phase and immunotherapy trialsat The Tisch Cancer Institute at Mount Sinai, New York, New York.

He and his colleagues are conducting aphase 1 clinical trial to assess the clinical efficacy and response of patientsto cemiplimab therapy in HCC, early-stage non-small cell lung cancer (NSCLC), andhead and neck squamous cell carcinoma (HNSCC). The team will investigate single-cellmapping of cancer lesions and circulating immune cells, spatial mapping of thetumor tissues, and sequencing of the patients microbiome before and aftertreatment.

What makes this investigation novel isthat it attacks the problem with a multipronged approach and combinesresearchers 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 ina diverse range of disease settings. We do not truly know how these agentswork in vivo. So, we are not able to identify rational combinatorial approachesin surgical patients or metastatic patients, Dr Marron told Cancer Therapy Advisor. We need toidentify biomarkers in order to identify who will benefit from therapy, so asto not waste our patients time, and cause unnecessary personal, physical, andfinancial toxicity.

He said in the metastatic setting, somepatients with HCC, NSCLC, or HNSCC have shown responses to immunotherapy. InNSCLC and HNSCC, the response rate to immunotherapy seems to increase whencombined with chemotherapy, but still, half of patients do not respond. Ourgoal is to use upfront immunotherapy to prime an immune response and decreasethe chance of recurrence, said Dr Marron. We believe that [in] patients withlocoregional disease, [and] with smaller, less heterogeneous tumors, there willlikely be a higher response rate than seen in the metastatic setting.

Excerpt from:
New Investigation Into PD-1 Blockade for Hepatocellular Carcinoma - Cancer Therapy Advisor