Marron is the director of the Early Phase Trials Unit at the Icahn School of Medicine at Mount Sinai, where he and his team are developing a neoadjuvant platform that allows them to explore the immunotherapy space, specifically window of opportunity studies. These studies are conducted by administering an immunotherapy for a short period of time, such as two to six weeks prior to patient surgery. The small trials contain only 10-15 patients per cohort and are designed to rapidly accrue data to propel the field forward.

By comparing tissue pre and post-surgery, the team can determine what is happening in patients and what role the immunotherapy is playing in those changes. This is important, Marron noted, because it helps researchers understand the basic principle of how standard-of-care therapies and immunotherapies work and, importantly, what single or rare subset of myeloid cells are being affected by those therapies.

Furthermore, Marron’s team is using high-resolution single-cell platforms, spatial transcriptomics platforms, and multiplexed immunohistochemistry tools to understand how drugs are affecting select subsets of cells involved in cancer and how those cells are perturbing the tumor microenvironment.

Ultimately, this will enable more intelligent decisions on which combination approaches to explore in larger populations, Marron said.

“We really don’t have enough patients to try every combination under the sun … in large phase II trials,” Marron explained. “We have to identify the most rational drugs to pursue in clinical trials so that we cannot spend the next 10-15 years for the next PD1 to be discovered and approved.”

What makes immunotherapies successful in one tumor but not in others?
Researchers have developed a new framework to uncover pathophysiological and molecular features that determine the effectiveness of immunotherapies. The...