Balixafortide (a CXCR4 antagonist) + eribulin in HER2-negative metastatic breast cancer (MBC): Survival outcomes of the phase I trial.

person Peter A. Kaufman Breast Oncology, Division of Hematology/Oncology, Burlington, VT info_outline Peter A. Kaufman, Sonia Pernas Simon, Miguel Martin, Marta Gil-Martin, Patricia Gomez Pardo, Sara Lopez-Tarruella, Luis Manso, Eva Ciruelos, Jose Alejandro Perez-Fidalgo, Cristina Hernando, Foluso Olabisi Ademuyiwa, Katherine N. Weilbaecher, Ingrid A. Mayer, Timothy J. Pluard, Maria Martinez Garcia, Linda T. Vahdat, Debra Barker, Barbara Romagnoli, Javier Cortes

Authors person Peter A. Kaufman Breast Oncology, Division of Hematology/Oncology, Burlington, VT info_outline Peter A. Kaufman, Sonia Pernas Simon, Miguel Martin, Marta Gil-Martin, Patricia Gomez Pardo, Sara Lopez-Tarruella, Luis Manso, Eva Ciruelos, Jose Alejandro Perez-Fidalgo, Cristina Hernando, Foluso Olabisi Ademuyiwa, Katherine N. Weilbaecher, Ingrid A. Mayer, Timothy J. Pluard, Maria Martinez Garcia, Linda T. Vahdat, Debra Barker, Barbara Romagnoli, Javier Cortes Organizations Breast Oncology, Division of Hematology/Oncology, Burlington, VT, Institut Català D'Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain, Hospital General Universitario Gregorio Marañón, Instituto Investigación Sanitaria Gregorio Marañón, Madrid, Spain, Institut Català d'Oncologia-ICO L’Hospitalet, Barcelona, Spain, Breast Cancer Center, Vall d'Hebron University Hospital, Barcelona, Spain, Instituto de Investigación Sanitaria Gregorio Marañón, Spain, Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, GEICAM Spanish Breast Cancer Group, Madrid, Spain, Medical Oncology Department. Hospital 12 de Octubre, Madrid, Spain, Hospital Universitario 12 de Octubre, Madrid, Spain, Department of Hematology and Medical Oncology, INCLIVA, University of Valencia, Valencia, Spain, Hospital Clínico Universitario de Valencia, Valencia, Spain, Washington University School of Medicine in St. Louis, St. Louis, MO, Vanderbilt-Ingram Cancer Center, Nashville, TN, St Luke's Cancer Institute, Kansas City, MO, Hospital Del Mar, Barcelona, SC, Spain, Weill Cornell Medicine, New York, NY, Polyphor, Allschwil, Switzerland, Polyphor, Ltd, Allschwil, Switzerland, IOB Institute of Oncology, Quironsalud Group, Madrid and Barcelona, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Balixafortide (B) is a potent antagonist of the chemokine receptor CXCR4. Preclinical evidence suggests that disrupting CXCR4 dependent pathways prevents development of breast cancer metastases, enhances the cytotoxic effect of chemotherapy and immunotherapy, and counteracts tumor cell evasion of the immune system. Encouraging safety and efficacy data were published recently from the ongoing Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC (Pernas S. et al. Lancet Oncol. 2018; 19: 812−24). The objective response rate, median progression free survival and median overall survival (OS) for the expanded cohort (EC) and the overall efficacy population (OEP) were 37.5% and 29.6%, 6.2 months and 4.5 months, and 18 months and 16.8 months, respectively. Here we report the 18 and 24 months landmark OS data from this trial. Methods: This trial enrolled 56 patients with HER2-negative, CXCR4-positive MBC, previously treated with 1−3 chemotherapy regimens for MBC. A 3+3 dose escalation design was used, followed by an EC. All cohorts received E on days 2 and 9, and B on days 1−3 and 8−10 of 21 day cycles. The association between various baseline biomarkers and treatment outcomes including OS is currently being investigated in a multivariate analysis (MVA). Results: Landmark survival data for the trial are shown in the table. Clinical trial information: NCT01837095 Conclusions: Landmark 18 months and 24 months OS data are consistent with the positive trend of all efficacy read-outs observed in this study and safety information is consistent with what was previously reported. Although inter-trial comparisons should be interpreted with caution, these survival rates, especially for the EC, are higher than those reported for eribulin monotherapy in similar MBC populations. These promising results suggest that B + E could potentially provide a new treatment option in heavily pre-treated patients with HER2 negative MBC and this is currently being investigated in a pivotal, randomized trial. Landmark (months) OS for EC (95% CI) OS for OEP (95% CI) 18 50% (29.1–67.8) 42.4% (28.9–55.2) 24 33.3% (15.9–51.9) 25% (14.3–37.3) The results from the MVA will be presented at the meeting.