Abstract PS12-13: Balixafortide (a CXCR4 antagonist) plus eribulin in HER2 negative metastatic breast cancer: Final analysis from the Phase 1 single arm trial
Authors: Kaufman Peter A. , Pernas Sonia , Martin Miguel , Gil-Martin Marta , Pardo Patricia Gomez , Lopez-Tarruella Sara , Manso Luis , Ciruelos Eva , Perez-Fidalgo Jose Alejandro , Hernando Cristina , Ademuyiwa Foluso O , Weilbaecher Katherine , Mayer Ingrid A , Pluard Timothy J. , Garcia Maria Martinez , Ringeisen Francois , Schmitter Daniela , Cortes Javier 
Published: February 2021

Abstract
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 safety and efficacy analyses from this trial, including an assessment of dose-response and adverse events of particular interest (AEPIs) (e.g. neutropenia, peripheral neuropathy).
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 B doses (0.5−1mg/kg) + increasing E doses (1.1−1.4mg/m2); Part II dose-escalation cohort for B (1−5.5mg/kg) + 1.4mg/m2 E; Expanded Cohort (EC) to confirm safety and efficacy of B 5.5mg/kg + 1.4mg/m2 E. Most cohorts received E on days 2 and 9, and B on days 1−3 and 8−10 of 21-day cycles.
Results: At entry, all 56 women (age range 33−82 years) were HER2 negative, CXCR4 positive. Most pts were Caucasian and heavily pretreated 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.
A linear dose-exposure was observed over the entire dose range tested for B. Cmax and AUC for E were within published ranges.
Safety findings (including AEPIs) remained similar to those reported previously1.
No dose-limiting toxicities were confirmed; therefore, the maximum tolerated dose of B was not reached. The highest B dose evaluated was 5.5mg/kg; pharmacokinetic evaluation showed that further protocolled dose increments of B would not have provided a sufficient increase in plasma levels. In addition, the objective response rate in Part II was 3-fold greater than published for eribulin alone which suggested that the anti-tumor activity of B was worthy of further exploration at 5.5mg/kg in the EC.
Efficacy data for the trial are shown in the table.
These data suggest a potential dose-response relationship for B across all efficacy endpoints, with efficacy being numerically greatest in the EC. While PFS and OS should be interpreted with caution in single arm trials, these data suggest potential benefit for this combination. Further analyses will be presented.
Responses were observed regardless of line of chemotherapy on study or extent of CXCR4 expression and were numerically higher in hormone receptor positive patients.
Conclusions: A consistent dose response effect for B + E was suggested across all efficacy endpoints for heavily pretreated pts with HER2 negative MBC. When these results are compared with published data for E monotherapy in similar populations, the EC consistently shows numerically greater benefit for all efficacy endpoints2, 3.
The safety and tolerability of B + E appear comparable to published data on E or B alone, particularly for neutropenia and peripheral neuropathy1.
These results suggest that B + E could potentially provide a new treatment option in heavily pretreated patients with HER2 negative MBC. A Phase 3 trial exploring efficacy and safety of B 5.5mg/kg + E is ongoing.
1. Pernas S et al. Lancet Oncol. 2018; 19: 812−242. Cortes J et al. Lancet. 2011; 377: 914−9233. Kaufman PA et al. J Clin Oncol. 2015; 33: 594−601
Part II(N=21)Expanded Cohort(N=24)Overall Efficacy Population(N=54)Objective Response Rate (95% CI)33% (15−57)38% (19−59)30% (18−44)median duration in months (IQR)2.8 (1.4−3.3)4.4 (3.1−5.3)3.2 (2.2−4.5)Clinical Benefit Rate (95% CI)43% (22−66)63% (41−81)44% (31−59)median duration in months (IQR)5.4 (4.2−6.7)8.1 (6.3−10.8)6.9 (5.4−10.3)median PFS in months (95% CI)4.2 (3−5.4)6.2 (2.9−8.1)4.6 (3.2–5.7)median OS in months (95% CI)10.4 (7.7−18.4)18 (12.2–27.2)16.8 (10.6–18.4)Landmark OS estimate12 months (95% CI)40% (19−60)75% (53−88)60% (45−72)18 months (95% CI)30% (12−50)50% (29−68)42% (29−55)24 months (95% CI)20% (6−39)33% (16−52)25% (14−37)CI: confidence interval; IQR: interquartile range; OS: overall survival; PFS: progression free survival
Citation Format: Peter A. Kaufman, Sonia Pernas, Miguel Martin, Marta Gil-Martin, Patricia Gomez Pardo, Sara Lopez-Tarruella, Luis Manso, Eva Ciruelos, Jose Alejandro Perez-Fidalgo, Cristina Hernando, Foluso O Ademuyiwa, Katherine Weilbaecher, Ingrid A Mayer, Timothy J. Pluard, Maria Martinez Garcia, Francois Ringeisen, Daniela Schmitter, Javier Cortes. Balixafortide (a CXCR4 antagonist) plus eribulin in HER2 negative metastatic breast cancer: Final analysis from the Phase 1 single arm trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-13.