Phase 1/2 study of glucocorticoid receptor (GR) antagonist mifepristone (MIFE) in combination with eribulin (E) in advanced solid tumors, with dose expansion in patients with GR-positive (GR+) triple-negative breast cancer (TNBC).

Abstract

e12550Background: GR is highly expressed in TNBC and is associated with a poor prognosis in estrogen receptor-negative (ER-) early stage breast cancer. Treatment with MIFE potentiates the effects of chemotherapy (ctx) in TNBC xenografts. Here we describe the results of an ongoing trial including outcomes to date in all patients with GR+ TNBC treated at the recommended Phase 2 dose (RP2D). Objectives: To determine the safety, tolerability, pharmacokinetics (PK) and clinical activity of the MIFE+E combination in pts with GR+ TNBC at the RP2D. Methods: Eligibility: Phase 1, pts with solid tumors; Phase 2, pts with GR+ TNBC; up to 5 prior ctx regimens for advanced disease; ECOG PS 0-1; adequate end-organ function. Design: 3 + 3 dose escalation scheme. After a 7-day lead-in of oral daily MIFE alone, MIFE was continued daily and E was given on days 1 and 8 of a 21-day cycle. Results: 16 pts with metastatic breast cancer were enrolled in Phase 1 (3 with GR+ TNBC). MTD/RP2D was MIFE 300 mg/day + E 1.1 mg/m2. To d...