Abstract
5590 Background: The FDA approval of pembrolizumab for patients with MSI-H or dMMR tumors has led to the treatment of a select cohort of endometrial cancer (EC) patients. We sought to ascertain tumor immune modulatory effects in the front-line setting for advanced stage III/IV EC patients regardless of MSI-H or dMMR. The primary objective was to determine the safety of preoperative and maintenance pembrolizumab. The secondary objective was to examine pembrolizumab-induced changes in peripheral immune effector phenotype in order to identify potential biomarkers of clinical response. Methods: In an open label, single-arm Phase I trial, 8 EC patients were treated with 2 doses of preoperative pembrolizumab IV prior to surgery followed by chemotherapy and 4 doses of pembrolizumab IV. As an initial study, pre- and post-treatment (on the day of surgery) peripheral blood was collected from 3 patients as well as a healthy control and processed for high-dimensional single-cell mass cytometry (CyTOF) using an optimized antibody panel. Results: Six of 8 patients completed the treatment. One patient had rapid cancer progression and another had an exacerbation of comorbidities. Peripheral blood from 3 patients with pathological response were then immunoprofiled using CyTOF. Data analysis revealed that the frequencies of CD8+ T cells, B cells and CD56hiCD16- NK cells were lower, whereas the frequency of CD14+CD16-HLA-DRhi classical monocytes was higher in the cancer patients compared to controls. Cancer patients had lower frequencies of circulating CD4+ and CD8+ naïve T cells but higher frequencies of effector CD8+ and CD4+ T cells. Notably, the median expression of Granzyme B in CD8+ and CD4+ T cells was higher and median expression of signal regulatory protein (SIRP), CD172a-b on monocytes was lower for cancer patients compared to control. The frequencies of NK and myeloid cells expressing CD137(4-1BB), PD-1+NK cells, and PD-L1+DCs were greater in post-compared to pre-pembrolizumab. Conclusions: This is the first trial to evaluate the use of neoadjuvant pembrolizumab in advanced stage EC patients. Here, we present peripheral immune correlative data and show an increase in markers of activation in patients with pathologic responses to pembrolizumab. Additional data from this ongoing study will help us to identify candidate predictive biomarkers. Clinical trial information: NCT02630823.
Published Version
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