An Exploratory Study of Pembrolizumab Plus Entinostat in Non-Inflamed Stage III/IV Melanoma
Status:
Recruiting
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
Summary
Cancers develop in two different ways. First, cancer cells can become invisible to the immune
system by stop having proteins on their surface that are required for the immune system to
recognize them. In this scenario, tumors do not attract any immune cells (e.g. white blood
cells) whatsoever or they do not attract specialized white blood cells against cancer cells,
called lymphocytes. White blood cells are the type of immune cells that attack foreign cells,
such as cancer cells or normal cells infected with viruses or bacteria. Second, cancer cells
can still grow side-to-side with white blood cells but are able to hide from them. As a
result, the white blood cells cannot find and attack the cancer cells. Different types of
cancers have different chance of having immune cells in the tumor. For example, the
possibility that immune cells are within skin melanomas is almost 50% whereas the possibility
in melanoma of the eye is only 10%.
As a result, the first goal of this study is to understand whether entinostat can make a
melanoma tumor more visible to the immune system. To see whether entinostat makes tumor more
visible to the immune system, participants will have a mandatory tumor biopsy 3 weeks after
starting entinostat therapy. Tumor tissue collected before and after participating in this
study will be compared to see if there are more immune cells in the tumor after receive
entinostat. The second goal of the study is to see if giving a combination of entinostat and
pembrolizumab can shrink melanoma tumors of patients who did not have immune cells in tumors
prior to treatment. The study will determine how many subjects cancer has become better or
not changed 6 months after subjects have started treatment on the study. We will also
determine what type of side effects occur in subjects receiving entinostat and pembrolizumab
to look at the safety of this combination.
The investigators will also look at any changes in the DNA of melanoma before the study
begins. As a result of these changes in DNA, there are often see differences in the proteins
that work to create other proteins. In addition, the study will look into how entinostat may
make melanoma cells more visible to the immune system by comparing proteins in tumors before
and after treatment. Finally, the study will see if this treatment changes the numbers and
types of immune cells that are found in the blood by comparing blood at different time points
while patients are on the study.