Neoadjuvant Cemiplimab Study: Identifying Better Biomarkers to Target Head and Neck Cancers

Researchers at the Tisch Cancer Institute’s Novel Therapeutics Unit (NTU) are conducting an exclusive clinical study to determine the clinical activity and safety of a preoperative immunotherapy treatment, cemiplimab (Libtayo), in patients with resectable non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and head and neck squamous cell carcinoma (HNSCC) lesions. The drug was previously studied at Mount Sinai in liver and lung cancer patients, and is currently approved by the FDA for patients with metastatic cutaneous squamous cell carcinoma (CSCC).

“With immune therapies we are essentially vaccinating patients against their own disease,” says Thomas Marron, MD, PhD, Assistant Professor of Hematology and Medical Oncology, Assistant Director of Early Phase and Immunotherapy Clinical Trials, and Principal Investigator of the study. “The idea behind cemiplimab is that it recruits and provokes the immune system to learn there is a tumor, recognize it as foreign, and ultimately kill any residual cells—termed micro-metastatic disease—that have escaped the primary tumor and would not be removed during surgery.”

About the Neoadjuvant Cemiplimab Study

Physicians know immunotherapy treatment works for a subset of head and neck cancer patients. But why it works, and for which patients, is not fully understood. To learn more about why certain patients respond to treatment and others do not, Dr. Marron and his team are capitalizing on the “window of opportunity” before patients have their tumor removed. In the study, funded in part by the Cancer Research Institute:

  • Twenty-one participants will receive 3 to 6 weeks of neoadjuvant cemiplimab prior to surgery. Neoadjuvant therapies are delivered before a primary treatment, such as surgery.
  • Tissue, blood, and stool samples will be examined and compared throughout the duration of the study.
  • The effectiveness of the anti-tumor agent will be measured by evaluating the resected tumors.
  • After the procedure, participants will receive the standard treatment of chemo and/or radiation, as well as 8 additional cycles of immunotherapy.

Goals of the Study

  • To determine which patients would benefit from cemiplimab
  • To identify biomarkers by looking at responders, non-responders, and recurrence of disease.
  • To find markers that can predict what type of therapy patients need.

Cemiplimab and Biomarker Identification

Tumors often express a protein on the cell surface called PD-L1, which acts like a stop-sign to limit the ability of the immune system to recognize and kill cancer cells. PD-L1 binds the protein PD-1 on the surface of T cells (the most potent anti-cancer cells in your immune system), and turns off the T cells.

Cemiplimab works by inhibiting this interaction between PD-1 on T cells and PD-L1 on the tumor, disrupting the off signal induced by this “stop-sign.” There are six FDA-approved drugs disrupting this interaction; and there are hundreds of drugs in development targeting immune regulatory pathways other than PD-1/PD-L1; however, little is known about how to predict which drugs will work for which patients.   

Advances in Immune Monitoring Technologies

Prior to launching this study, Mount Sinai was one of four leading institutions that received a grant from the Cancer Immune Monitoring and Analysis Centers, part of the Cancer Moonshot initiative. These centers are responsible for developing standards to monitor all cancer trials sponsored by the National Institutes of Health (NIH).

Optimizing immune monitoring technology has been key to Mount Sinai’s success. Dr. Marron’s team is using several advanced techniques including:  

  • CyTOF – While we have used flow cytometry for years to characterize immune cells, this new platform also known as Mass Cytometry stains proteins on single cells by making antibodies that are stuck to heavy metals. Antibodies are proteins made by our immune system that are able to bind specific protein targets. Researchers can use this new technology to see up to 50 proteins on each individual cell, allowing them to identify the cell type, and classify the maturation and activation status of the cell, as well as some of the regulatory on/off checkpoints.
  • CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) — For an even higher-resolution view of each individual immune cell within the tumor, this technique combines the capabilities of CyTOF and single-cell RNA sequencing to characterize both the RNA and protein in each individual cell.
  • VelocImmune technologies —As part of a partnership with the study sponsor, Regeneron Pharmaceuticals, Mount Sinai researchers have access to a collection of technologies that were developed to better understand how antibodies could be created rapidly for potential therapeutics. Their collaboration allows the researchers to speedily study new targets, and find smarter ways to manipulate the immune system.