Hematology and Oncology 2022

Novel oral IRAK-4 inhibition plus checkpoint inhibition in metastatic melanoma

Faculty Mentor’s Name: Dr. Bently Doonan
Email: bently.doonan@medicine.ufl.edu
Phone Number: (843) 340-0085
Project Category: Translational
International Component or Travel: No

Research Project Description:

Metastatic melanoma is a growing clinical concern and has an increasing incidence both locally in our state and our nation. Current approaches utilize immunotherapy or targeted therapy in management of metastatic disease. Though effective in some, the majority of patients fail to see long term benefit and compounding this issue melanoma has the second highest incidence of brain metastases. Novel approaches to therapy are needed to overcome this issue.

This project is studying the preclinical and translational possibility of targeting melanoma brain metastases and peripheral systemic metastases using a novel oral IRAK-4 inhibitor CA-4948. This is a partially sponsored research study with support from the drug manufacturer Curis. This exploratory analysis looks to further describe and understand the interaction between CA-4948 with immune checkpoint inhibition namely anti-PD1 therapy. It looks to identify relevant biomarkers of response to treatment and aims to develop a bioassay for prediction of response to therapy and monitoring. This preclinical study also serves as the basis of a planned phase I/II clinical trial in patients with melanoma brain metastases.

Students involved in the project will get first hand experience on mouse models of metastatic melanoma, therapeutic drug evaluation, biomarker identification and tumor microenvironment analysis. This study will utilize advanced immunohistochemistry, bioassays, flow cytometry, and immune cell monitoring techniques. Should the clinical trial be up and running by summer 2022 which is the goal, there would be a potential for helping with recruitment and consenting of patients as well as patient sample analysis.