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 with a median days on study of 56 days (p = 0.01). Ten patients with
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 (
Clinical trial identification
Legal entity responsible for the study
Karyopharm Therapeutics, Inc.
M. Crochiere: I am a current employee of Karyopharm Therapeutics and own stock. I.B. Vergote: PI on a Karyopharm Clinical Study. B. Lund, H. Havsteen, Z. Ujmajuridze, C. Haslund, T. Juhler-Nøttrup, M. Mau-Sørensen, P. Berteloot: PI on a Karyopharm clinical study. E. Van Nieuwenhuysen: PI on a Karyopham clinical study. A. Kranich: Director of the CRO managing Karyopharm clinical study. J. Meade, G. Wright, E. Shacham, J-R. Saint-Martin: Current Karyopharm employee and stock holder. T. Rashal: Former Karyopharm employee and stock holder. S. Shacham, M. Kauffman: Owner of Karyopharm and stock holder. M. Raza Mirza: Karyopharm board member and stock holder. Y. Landesman: Current employee of Karyopharm and stock holder.