Funded by the Stuart Scott Memorial Cancer Research Fund
Antibody treatments that block ‘immune checkpoints’ which prevent the immune system from fighting cancer, have resulted in impressive tumor shrinkage and long term survival in many patients with cancer. Results from studies in metastatic triple-negative breast cancer (TNBC) indicate promising activity but not yet the exceptional results seen in tumors known to be highly “immunogenic” or responsive to alterations in the immune system. Strategies to make TNBC “immunogenic” are therefore of great interest as they may result in long term control of TNBC. This is of particular relevance to minority groups such as the African American population, who often present with an aggressive TNBC with limited treatment options available.
Our collaborators at Johns Hopkins have laboratory data, suggesting that combining the histone deacetylase (HDAC) inhibitor entinostat with immune-checkpoint blockade (nivolumab and ipilimumab) led to eradication of breast tumors and long term cures. Research suggests that entinostat may alter the tumor environment by affecting the regulatory immune cells which can prevent immune-checkpoint agents from fighting cancer. This combination may thus be able to convert these traditionally “non-immunogenic” tumors into tumors which can respond to immune therapy.
We are thus conducting a phase I clinical trial of entinostat, nivolumab +/- ipilimumab in advanced solid tumors and patients with TNBC. We anticipate that the collection of blood and tumor specimens during the study will allow us to determine how these drugs are working in patients so we can develop future trials with the hope of significantly improving outcomes for patients with TNBC.