The ultimate goal of the study is to identify potential biomarkers, immune gene expression signatures, and co-stimulatory pathways that may be used to understand the effect of immune checkpoint inhibitors on gynecologic cancers.
Epithelial gynecologic malignancies are tumors of müllerian origin, which include ovarian, endometrial, fallopian tube, and primary peritoneal cancers, and account for \>70,000 new diagnoses and \>22,000 deaths per year in the United States alone. Treatment typically consists of a thorough cytoreductive and staging surgery in combination with platinum/taxane chemotherapy. Newer approaches adding anti-angiogenic therapies to chemotherapy have resulted in moderate improvements in recurrence free survival. However, despite these aggressive treatments, the majority of women with advanced stage at diagnosis will experience relapse. Unfortunately, relapsed disease is incurable and women ultimately die of their disease despite maximal efforts at cancer control using subsequent chemotherapy or targeted agents. There has been significant interest in incorporating immune checkpoint therapies in the treatment of gynecologic malignancies, especially given the durable remissions associated with these therapies in the treatment of melanoma and early indications of durable responses in recurrent ovarian cancer. At this time, little is known about whether or how to combine chemotherapy, anti-angiogenic therapies, and immunologic therapies for maximal benefit. Understanding the tumor microenvironment, particularly immune and angiogenic factors that contribute to tumor survival, as well as the changes that occur in response to immunotherapy is critical to identify favorable biomarker profiles which could lead to improved prognostic outcomes and inform the development and sequencing of therapies to maximize benefit.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Pembrolizumab 200mg IV
Duke Cancer Institute
Durham, North Carolina, United States
Change in Tumor Immune Infiltrates as Measured by PD-L1 Modified H-Score
This outcome measures the change in tumor immune infiltrates post-pembrolizumab versus pre-pembrolizumab as measured by the PD-L1 Modified H-score. Histological score (H-score) is a score that is comprised of intensity and percentage of staining and is used for assessing amount of protein (in this case PD-L1) present in a tissue sample. H-score is determined by adding of the percentages of cell staining at each intensity level multiplied by the membrane intensity of staining (0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+(strong staining)). The H-score has a range of 0 to 300. Lower H-scores represent lower expression of PD-L1 in the tumor sample, while higher scores represent stronger expression of PD-L1 in the tumor samples.
Time frame: Baseline and 14-21 Days
Toxicity Profile: Frequency and Severity of Adverse Events as Assessed by CTCAE
Frequency and severity of adverse events associated with pembrolizumab when given to patients with newly diagnosed gynecologic cancers of müllerian origin prior to standard surgical therapy and as maintenance therapy after completion of chemotherapy. All events experienced within the AE reporting time frame deemed probably, possibly, or definitely related to study drug above the reporting threshold of 4%. Categorized by grade and frequency, defined using CTCAE 4.0 event name and grading.
Time frame: 18 months
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