Abstract PD13-01: Balixafortide (a CXCR4 antagonist)+eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer: An international, randomized, phase 3 trial (FORTRESS)
Authors: Kaufman Peter , Martin Miguel , Mayer Ingrid , Vahdat Linda , Pernas Sonia , Schmid Peter , McArthur Heather , Dent Rebecca , Rugo Hope S , Barrios Carlos , Bobirca Alexandra , Ringeisen Francois , Schmitter Daniela , Cortes Javier 
Published: March 2022

Background: Balixafortide (B), a synthetic cyclic peptide, is a potent selective CXCR4 antagonist with high affinity for the human CXCR4 receptor in pre-clinical studies and is currently being investigated in metastatic breast cancer (mBC). Encouraging safety and efficacy data were previously published from a Phase 1 trial investigating B + eribulin (E) in patients (pts) with human epidermal growth factor receptor 2 negative (HER2-) mBC. Methods: In this multicenter, open-label trial, pts were randomized 1:1 to receive B (5.5 mg/kg) + E (1.4 mg/m2) or E alone. Eligible pts had HER2- locally advanced or mBC and had previously received 1−4 lines of chemotherapy in the advanced setting. Pts with hormonal receptor positive (HR+) disease must have received ≥1 line of endocrine therapy. The primary efficacy endpoints included objective response rate (ORR) and progression free survival (PFS) in the ≥3rd line population and PFS in the overall population. Overall survival (OS) was a key secondary endpoint. Results: 432 pts (aged 29-82 years) were enrolled with 348 treated in the ≥3rd line setting. Most pts (66.4%) were treated in the 3rd or 4th line, 96.1% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and 35.6% had triple negative breast cancer. ORR and clinical benefit rate (CBR) data for the ≥3rd line population are presented in the table below.

PFS and OS were not improved in the 3rd line population [mPFS 3.5 months (m) vs 4.0 m; hazard ratio 1.07 (96% CI: 0.81, 1.41); interim mOS 11.0 m vs 11.2 m hazard ratio 1.08 (99.9% CI: 0.66, 1.77)]. Results were consistent in the overall population and per investigator assessment.For the overall safety population, serious treatment-emergent adverse events (STEAEs) (28% versus 26.5%), treatment-emergent adverse events (TEAEs) leading to death (6.9% versus 6.4%) and TEAEs ≥Grade 3 (68.3% versus 64.2%) were broadly similar between the two arms. Infusion Related Reactions (IRR) were reported in 43.6% of patients treated with B + E. Conclusions: In this Phase 3 randomized trial, no differences in ORR, CBR, mPFS, or mOS were observed for B + E compared to E alone in any population of HER2-mBC patients. Efficacy parameters for E alone were similar to those reported previously. The combination was B + E was well-tolerated overall.

≥3rd Line Population(N=330)B + E(N=162)E(N=168)Objective Response Rate (95% CI)Per Independent Review Committee13.0% (8.2, 19.1)13.7% (8.9, 19.8)Per Investigator13.6% (8.7, 19.8)13.1% (8.4, 19.2)Clinical Benefit Rate (95% CI)Per Independent Review Committee16.7% (11.3, 23.3)19.6% (13.9, 26.5)Per Investigator21.6% (15.5, 28.7)21.4% (15.5, 28.4)

Citation Format: Peter Kaufman, Miguel Martin, Ingrid Mayer, Linda Vahdat, Sonia Pernas, Peter Schmid, Heather McArthur, Rebecca Dent, Hope S Rugo, Carlos Barrios, Alexandra Bobirca, Francois Ringeisen, Daniela Schmitter, Javier Cortes. Balixafortide (a CXCR4 antagonist)+eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer: An international, randomized, phase 3 trial (FORTRESS) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD13-01.