359TiP International phase III trial: Balixafortide (a CXCR4 antagonist) + eribulin versus eribulin alone in patients with HER2-negative, locally recurrent or metastatic breast cancer (FORTRESS)

Balixafortide (B), a synthetic cyclic peptide, is a potent selective CXCR4 antagonist with a demonstrated high affinity for the human CXCR4 receptor in in vitro receptor binding studies. Disrupting CXCR4-dependent pathways may prevent development of breast cancer metastases, enhance cytotoxic effects of chemotherapy and immunotherapy, and counteract tumor cell evasion. Encouraging safety/efficacy data were published from a phase I trial investigating B + eribulin (E) in ≥2nd line patients with HER2-negative metastatic breast cancer (mBC)1:Table 359TiPExpansion Cohort (N=24)Overall Efficacy Population (N=54)Objective response rate (ORR)37.5%29.6%Median progression free survival (PFS) (months)6.24.5Median overall survival (OS) (months)1816.8Consequently, a phase III registration trial is ongoing. Open table in a new tab Consequently, a phase III registration trial is ongoing. International, multicenter, open-label, 2-arm trial. Patients are randomized in a 1:1 ratio to B + E or E alone. Eligible patients are aged ≥18 years; have mBC or unresectable locoregionally recurrent BC; histologically confirmed HER2-negative; and have previously received 1−4 chemotherapy regimens in the metastatic setting. Patients with ER+ and/or PgR+ disease must have received at least 1 line of endocrine therapy and be unsuitable for further endocrine therapy. Efficacy endpoints for the overall and ≥3rd line populations are PFS (primary) and OS (key secondary). ORR is a co-primary endpoint for the ≥3rd line population. The design allows for statistical success by meeting at least 1 efficacy endpoint (ORR, PFS or OS) in the ≥3rd line population or at least 1 (PFS or OS) in the overall (≥2nd line population), as prospectively defined considering the locally-approved eribulin label. Patients will be stratified according to: • Lines of chemotherapy (2nd vs. ≥3rd line) • Hormone receptor status • Previous CDK4/6 inhibitor treatment • Visceral vs. non-visceral disease on 22 April 2020, 259 patients from an accrual target of 384 were enrolled in 13 countries. Enrollment is open with completion anticipated by September 2020. 1. Pernas S et al. Lancet Oncol. 2018; 19: 812−24. NCT03786094. Linda Summerton; tranScrip Stacey Maxwell; tranScrip. Polyphor Ltd.