The purpose of this research study is to find the lowest dose of the cancer drug parsaclisib that has an effect on the type of breast cancer a participant has. Researchers are looking at how Parsaclisib affects the immune system. They want to learn whether and how it helps the immune system to find cancer cells to fight them. Parsaclisib is an oral drug that limits the effects of a protein called phosphatidylinositol 3-kinase δ (PI3K). By limiting P13K, parsaclisib can block certain cells that prevent the immune cells from working. As a result, it may help the body's immune system to fight tumors. Parsaclisib is being studied in several clinical trials to treat different types of cancers. Parsaclisib has not yet been approved by FDA for the treatment of cancer. Studies have shown that a good way to find out how cancer acts when exposed to anti-cancer drugs is through a pre-operative window study. In this type of study, tissue and blood are collected before treatment. Then subjects receive a study drug for a few weeks before surgery. Blood is drawn during the course of treatment, and leftover tissue is collected during surgery. Comparing the tissue and blood before and after treatment shows the effects the study drug may have had on the tumor. Research shows that cancers differ when you look at the DNA and RNA (genetic codes) that are inside a cancer cell. DNA and RNA carry genetic information that can determine traits in humans (such as eye color, height, reaction to treatment, etc.), as well as the traits of cancer cells. Depending on the genetic profile (particularly DNA and RNA) of the cancer, it may respond differently to parsaclisib. In this study, the investigators will look at the genetic profile of a participant's tumor by studying tissue and blood samples collected before and after receiving treatment.
Name: Parsaclisib
Description: To determine the minimum dose of parsaclisib, administered once daily for 14 consecutive days, needed in subjects with triple-negative or human epidermal growth factor receptor 2 (HER2) positive breast cancer to result in either a 50% increase in the intratumoral cluster of differentiation 8 (CD8+) Thymus (T) cells/regulatory T cell ratio or a 50% decrease in the percentage of intratumoral regulatory T cells as measured using single cell transcriptomics and/or flow cytometry.
Measure: Minimum effective dose of parsaclisib Time: At time of surgery (2 weeks after start of parsaclisib)Description: To determine the minimum dose of parsaclisib, administered once daily for 14 consecutive days, in subjects with triple-negative or HER2 positive breast cancer resulting in either a 50% increase in the peripheral blood CD8+ T cells/regulatory T-cell ratio or a 50% decrease in the percentage of peripheral blood regulatory T cells as measured using single cell transcriptomics and/or flow cytometry.
Measure: Minimum dose of parsaclisib needed to decrease peripheral blood regulatory T cells Time: At time of surgery (2 weeks after start of parsaclisib)Description: To identify changes in the regulatory T cell signature following treatment with parsaclisib in subjects with triple-negative or HER2-positive breast cancer. A regulatory T-cell gene signature expression score is defined as the average of upper quartile normalized and log2 transformed gene expression values of all genes belonging to that gene signature was calculated for each sample. Gene expression values will be determined via RNA-sequencing. A one-sided paired t-test will be used to test for significant pre-post reductions in signature values in each subject, reflecting a decrease in the abundance of intratumoral regulatory T cells.
Measure: Changes in regulatory T cell signature Time: At time of surgery (2 weeks after start of parsaclisib)Description: To identify changes in Ki-67 messenger Ribonucleic acid (mRNA) expression following treatment with parsaclisib in subjects with triple-negative or HER2-positive breast cancer. Ki-67 expression pre versus post treatment will be assessed using the average log2 fold change in gene expression between conditions.
Measure: Changes in Ki-67 mRNA expression Time: At time of surgery (2 weeks after start of parsaclisib)Description: The reduction in the regulatory T cell signature by dose of parsaclisib (10 mg, 3.0 mg or 1.0 mg) will be measured as Pre and post-treatment levels of regulatory T-cell total abundance (cell count) and relative abundance (percentage of all cells), and change in relative abundance (fold change in % abundance post vs pre-treatment)
Measure: Comparison of reduction in the regulatory T cell signature by dose of parsaclisib Time: At time of surgery (2 weeks after start of parsaclisib)Allocation: N/A
Single Group Assignment
There is one SNP
By limiting P13K, parsaclisib can block certain cells that prevent the immune cells from working. --- P13K ---