Overall survival in a trial of orally administered CCR2 inhibitor CCX872 in locally advanced/metastatic pancreatic cancer: Correlation with blood monocyte counts.

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Background: The CCL2-CCR2 signaling axis may facilitate migration of myeloid derived suppressor cells to pancreatic cancer resulting in an immune suppressive tumor microenvironment. CCR2 inhibition in patients with non-metastatic pancreatic cancer was previously reported to decrease tumor-infiltrating macrophages/Treg cells and increase effector T cells (Nywening et al, 2016). Here, a CCR2 specific antagonist CCX872 was used in combination with FOLFIRINOX to treat subjects with locally advanced or metastatic, non-resectable pancreatic cancer in a multi-center study. Methods: Fifty subjects (ECOG score ≤ 2) were enrolled, receiving FOLFIRINOX (fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) once every two weeks (maximum 12 cycles) plus 150 mg CCX872 QD or BID for 12 weeks. Subjects showing at least stable disease at the end of the 12-week treatment period were eligible to CCX872 treatment until disease progression. In this ongoing study, all subjects are followed for overall survival (OS). Blood samples were taken at baseline and at intervals throughout the active treatment period for hematologic and flow cytometric analysis of circulating immune cell populations. Results: The all-subjects OS at 18 months is 29%. This compares favorably with previously published data: i.e., OS of only 18.6% at 18 months for FOLFIRINOX regimen alone (Conroy et al, 2011). Peripheral blood monocyte counts at baseline inversely correlate with OS (p = 0.0071, Hazard ratio = 1.169) with CCX872 and FOLFIRINOX combination therapy. Overall, circulating monocytes, inflammatory monocytes and monocytic myeloid derived suppressor cells were reduced by treatment. Conclusions: CCX872-B plus FOLFIRINOX resulted in an OS of 29% at 18 months with no safety issues. Better OS was associated with lower peripheral blood monocyte counts at baseline. Clinical trial information: NCT02345408.