Abstract OT1-08-06: International, phase 3 trial: Balixafortide (a CXCR4 antagonist) + eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer (FORTRESS) international, phase 3 trial: Balixafortide (a CXCR4 antagonist) + eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer (FORTRESS)

Background: Balixafortide (B) is a potent CXCR4 antagonist. High CXCR4 levels correlate with aggressive metastatic phenotypes and poor prognosis in breast cancer (BC). Encouraging safety and efficacy data were published from the Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative metastatic BC1,2. The objective response rate (ORR), median progression free survival (PFS), median overall survival (OS), and 12, 18 and 24 month OS estimate in patients who received B + E as 2nd line or later therapy were respectively: 37.5%, 6.2 months, 18 months, 75%, 50%, and 33.3% for the Expanded Cohort (EC); 29.6%, 4.5 months, 16.8 months, 62%, 42.4%, and 25% for the Overall Efficacy Population. These OS data were observed regardless of line of study medication received and were numerically higher for patients who received study medication as 2nd line or later therapy. Inter-trial comparisons suggest that these survival rates, especially for EC, are higher than those reported for E monotherapy in similar populations. The following trial was designed and open to enrolment. Trial design: International, multicenter, open-label, randomized, parallel, 2 arm, Phase 3 Eligibility criteria: Age ≥18 years Histologically confirmed BC Metastatic BC (stage IV disease by AJCC criteria) or unresectable locoregionally recurrent BC HER2 negative Any estrogen or progesterone receptor (ER/PgR) status Previously received 1−4 chemotherapeutic regimens for locally recurrent or metastatic BC. Unless contra-indicated, prior therapy included an anthracycline and a taxane in either the adjuvant or metastatic setting. ER+ and/or PgR+ patients treated with at least 1 line of endocrine therapy and unsuitable for further endocrine therapy. At least 14 days from completion of previous cytotoxic chemotherapy, biological therapy, or other investigational agent Refractory to most recent chemotherapy (progression on ≤6 months of therapy) ECOG performance status 0−2 Life expectancy ≥3 months If CNS involvement, metastases must have been treated and stable for at least 4 weeks after completion of radiation therapy and/or surgery Patients with no concurrent malignancy or malignancy 2 years prior to randomization except for adequately treated basal and squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer. Aims: to investigate the comparative efficacy and safety of B + E versus E monotherapy in terms of: PFS in the Overall Study Population and in the 3rd Line or Later Therapy Study Population OS Tumor response Safety and tolerability Quality of life Exploring the association between comparative efficacy and ER or PgR status, CXCR4 expression levels, circulating and tumor tissue biomarkers Exploring immune response using iRECIST Evaluating pharmacokinetics of balixafortide and its metabolites. Statistical Methods: To provide efficacy and safety data in: Overall Study Population for regulatory submissions in the EU and jurisdictions in which the 2nd line + E label applies. 3rd line or Later Therapy Study Population for regulatory submissions in the US and jurisdictions in which the 3rd line + E label applies. The critical efficacy endpoints for both study populations are PFS and OS and additionally ORR for the 3rd line + Population. Alpha allocation and recycling will ensure control of the overall Type I error rate for the 2 study populations separately. Accrual: approx. 400 patients Contact information: Frank Weber MD Tel +41 61 567 1600 1. Pernas S et al. Lancet Oncol. 2018; 19: 812−24 2. Kaufman PA et al. J Clin Oncol. 2019; 37(Suppl 2606) Citation Format: Peter Kaufmann MD, Javier Cortes MD, PhD, Miguel Martin, MD, PhD, Ingrid Mayer MD, Linda Vahdat, MD, Sonia Pernas MD, PhD, Peter Schmid MD, PhD, Heather McArthur MD, Rebecca Dent MD, Hope Rugo MD, Carlos Barrios MD, Debra Barker MD, Barbara Romagnoli PhD and Alexandra Bobirca MD. International, phase 3 trial: Balixafortide (a CXCR4 antagonist) + eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer (FORTRESS) international, phase 3 trial: Balixafortide (a CXCR4 antagonist) + eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer (FORTRESS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-06.