886P - Circulating tumor cell number predicts time to progression (TTP) in patients with heavily pretreated gynecological cancers treated with selinexor (SEL)

Abstract

SEL, an oral, first-in-class selective inhibitor of XPO1-mediated nuclear export (SINE), induces nuclear retention and activation of tumour suppressor proteins including p53, BRCA1/2, CDKN2A and pRB. SEL has anti-cancer activity in preclinical models of cervical cancer (CC) & ovarian cancer (OC) and in a phase I clinical study. In an effort to identify markers predictive of disease control with SEL, circulating tumour cells (CTCs) were enumerated during the phase 2 trial from patients (pts) with heavily pretreated OC, CC & endometrial cancer (EC). NCT02025985. Patients with ≥ 2 lines of prior therapy, ECOG PS 0-1, were treated with single agent SEL. At predose C1D1, 7.5 mL of blood was collected in CellSave tubes and CTCs were identified using the Janssen Diagnostics CellSearch System. Intact cells that measured at least 4 microns in size and stained positive for DAPI, EpCAM, and cytokeratin while negative for CD45 were counted as CTCs. CTC were enumerated at predose C1D1 in 47 (33 OC, 8 EC, 6 CC) of 114 patients. To date, 31 pts had <2 CTCs at predose C1D1 with a median days on study of 108 days while 16 pts had >2 CTCs with a median days on study of 56 days (p = 0.01). Ten patients with <2 CTCs at predose showed stable disease for at least 12 weeks and 4 demonstrated partial response by RECIST 1.1. This study demonstrates that the presence of CTCs in pts prior to SEL treatment may correlate with a shorter TTP. Detection of CTC in the peripheral blood of cancer patients has proven feasible and of prognostic value in different neoplasms, including in patients with OC. These results suggest that low CTC count (<2) may also be used to identify pts with heavily pre-treated OC, CC & EC that may benefit from prolonged disease control with single agent oral single agent SEL. Additional studies are planned.