Balixafortide (a novel CXCR4 inhibitor) and eribulin in HER2-neg metastatic breast cancer (MBC) patients (pts): A phase I trial

Abstract

Background: CXCR4 is expressed in a variety of cancer types. The CXCR4/ SDF-1 axis plays a critical role in tumour growth, angiogenesis, metastasis and regulates function and trafficking of immune cells to the tumour microenvironment. CXCR4 antagonists enhance activity of different anti-cancer treatments in preclinical models. We assessed safety, tolerability and activity of the CXCR4 antagonist, balixafortide (B), in combination with eribulin (E) in heavily pre-treated MBC pts. Methods: This Phase I, open-label trial enrolled HER2-negative, CXCR4-positive MBC patients previously treated with 1-3 chemotherapy (CT) regimens for MBC. A 3+3 dose escalation design was used, followed by an Expanded Cohort. All cohorts received E on days 2 and 9, and B on days 1-3, and 8-10 of 21-day cycles. Results: Eleven cohorts were enrolled receiving B at 0.5-5.5 mg/kg. As no DLT was confirmed the MTD was not reached, so the highest B dose (5.5mg/kg) cohort was expanded to 24 pts. In the overall population, median age was 55.5 [33-82] years and median number of prior CT regimens for MBC was 2. TNBC pts were 13 (23%). Most common Gr 3-4 AEs were neutropenia (23 [41%]) and febrile neutropenia (6 [11%]). Two (3.6%) pts died due to septic shock and pneumonia. Anti-tumour activity is summarised in the table. Conclusions: This is the first trial to investigate a CXCR4 antagonist in MBC. The tolerability profile and promising anti-tumor activity observed with B + E in this Phase I study warrants further investigation as well as exploration of additional combinations of B with other anti-cancer therapies. (Table Presented) .