A New Idea for Advancing Axitinib-Based Therapy in Recurrent and Metastatic HNSCC
Abstract
This application focuses on fiscal year 2022 (FY22) Peer Reviewed Cancer Research Program (PRCRP) Topic Area Head and Neck Cancer. Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer with 800,000 new cases each year and poor overall survival for the majority of patients. Treatment options are extremely limited for these patients; and even with the success of recently developed immune-based therapies called immunotherapies, overall survival remains low for most patients. Our long-term objective is to develop new treatment strategies that improve the survival of patients with HNSCC. Recently, we completed a Phase 2 trial of a drug called axitinib in patients with recurrent and metastatic HNSCC. We found that patients whot had tumor mutations in a specific group of genes belonging to the PI3K pathway had significantly better responses to axitinib than patients with tumors that did not have a mutation in this group of genes. Importantly, about 45 to 55% of all HNSCC cancer patients have a mutation in the PI3K pathway, suggesting that almost half of all patients could benefit from this treatment. Therefore, we now propose to test if mutations in the PI3K pathway can be used to select patients for this therapy. Such a test could be easily done for patients. This would help identify patients who are most likely to benefit from axitinib, while allowing patients that do not have one of the mutations to choose other therapies more likely to work for them. Additionally, while clinical trials have shown that a new class of drugs mentioned previously called immunotherapies work well for about 20% of patients, we also propose to focus on the other 80% of patients for which immunotherapies do not work. To do this, we will also test a new approach to pre-treat tumors that are normally not responsive to immunotherapy with drugs that include axitinib, in an attempt to make them susceptible to immunotherapy. If we are able to successfully re-program a tumor such that existing therapies can now kill it, our research could represent a major step forward for patients who are currently without good treatment options. Long term, we hope that this pre-treatment strategy that we are calling a priming approach might represent a generalizable approach that could also be tested in other cancer in the future. This application will therefore focus on the following two FY22 PRCRP Overarching Challenges: (1) Transform cancer treatment through the identification of new targets, especially for advanced disease and metastasis, by working to identify new drug targets (which axitinib-regulated kinase is critical for survival of PI3K mutant cancers); and (2) Advance immunotherapy across the different PRCRP Topic Areas. Specifically, we will address challenge we will address challenge (2) by evaluating the potential of new immunotherapy combination therapies to improve survival.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310811
Entities
People
- John Brenner
Organizations
- United States Army
- University of Michigan