Balixafortide (A Cxcr4 Antagonist) Plus Eribulin In Her2 Negative Metastatic Breast Cancer: Dose-Response Analysis Of Efficacy From Phase I Single-Arm Trial.

e15209 Background: Balixafortide (B) is a potent, selective antagonist of the chemokine receptor CXCR4. High CXCR4 levels correlate with aggressive metastatic phenotypes and poor prognosis in metastatic breast cancer (MBC). Efficacy and safety data were published recently from the Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC1. We report the final efficacy analyses from this trial, including assessment of dose-response. Methods: In this single-arm, dose escalation trial, patients (pts) received E + increasing doses of B using a 3+3 design in 3 parts: Part I (cohorts received low E doses); Part II (dose-escalation cohort for B [1−5.5mg/kg] + 1.4mg/m2 E); Expanded Cohort (EC; 5.5mg/kg B + 1.4mg/m2 E) to confirm safety and efficacy. Results: At entry, all 56 women (age range 33−82 years) were HER2-negative (IHC and/or FISH), CXCR4 positive. The majority were Caucasian. Most pts were heavily pre-treated in the metastatic setting (line of chemotherapy on study: 29% 2nd line, 50% 3rd line, 21% 4th line). 75% were hormone receptor positive and 23% had triple negative breast cancer. Conclusions: A consistent dose response effect for B + E was suggested in heavily pretreated pts with HER2 negative MBC across all efficacy endpoints. A comparison of these efficacy results, and particularly response data, with single agent data for E in similar populations2, 3 showed that pts in the EC had a more profound benefit observed consistently throughout all efficacy endpoints. Further data and analysis will be forthcoming for presentation. 1. 3 patients from Part II also included in EC because they received the B dose selected for EC (5.5mg/kg). 2. Part I was an initial safety run-in with lower E doses, and so is not included in the table. 1. Pernas S et al. Lancet Oncol. 2018; 19: 812−24 2. Cortes J et al. Lancet. 2011; 377: 914−923 3. Kaufman PA et al. J Clin Oncol. 2015; 33: 594−601. Clinical trial information: NCT01837095 . [Table: see text]