Phase I study of the combination of balixafortide (CXCR4 inhibitor) and eribulin in HER2-negative metastatic breast cancer (MBC) patients (pts).

Abstract

2555 Background: Balixafortide (POL6326) is a cyclic peptide and a potent, selective antagonist of the chemokine receptor CXCR4. Evidence suggests that CXCR4 inhibition interferes with the tumor-protective microenvironment and sensitizes tumor cells to chemotherapy. The combination of balixafortide (B) and eribulin (E) was safe with early signs of efficacy in the dose escalation part of this study. Methods: The expanded cohort of thisopen label phase I study was designed to assess the anti-tumor activity, safety and pharmacokinetics of the addition of the recommended phase 2 dose (RP2D) of B to E in pts with MBC and with any CXCR4 expression level at the tumor site. Patients received E (1.4 mg/m2) on days 2 and 9, flanked by B (5.5 mg/kg) on days 1-3, and 8-10 of 21-day cycles. Results: 24 pts with relapsed MBC (median age 59 [33-82]) were enrolled in the expanded cohort. Median number of prior chemotherapies for MBC was 2 (range 1-3). 20/24 (83%) pts were ER and/or PR positive; 3/24 (13%) pts had TNBC. Objective response rate (ORR) was 33%. 8/24 (33%) pts achieved a partial response and 4/24 (17%) pts had meaningful (≥ 6 months) stable disease for a Clinical Benefit Ratio of 50%. Median duration of treatment was 15.3 weeks (range 5-40) with 11 pts still on treatment. The most common Gr 3-4 adverse events were neutropenia (9/24, 38%) and leucopenia (3/24, 13%); 2 pts had febrile neutropenia and 1 patient died from sepsis. 15/24 (63%) pts experienced histamine-like infusion reactions related to B that were manageable with anti-histamines. Conclusions: The therapeutic activity of this treatment regimen appears promising with an ORR of 33% in patients with advanced MBC. B (5.5 mg/kg) can be combined safely with E (1.4 mg/m2) and the safety profile resembles E monotherapy as previously reported. This is the first study of the treatment combination of E with B in relapsed MBC pts. Further confirmatory studies are being considered. Clinical trial information: NCT01837095.