CXCR4 is expressed in a variety of cancer types. The CXCR4/ SDF-1 axis plays a critical role in tumour growth, angiogenesis, metastasis and regulates function and trafficking of immune cells to the tumour microenvironment. CXCR4 antagonists enhance activity of different anti-cancer treatments in preclinical models. We assessed safety, tolerability and activity of the CXCR4 antagonist, balixafortide (B), in combination with eribulin (E) in heavily pre-treated MBC pts.
This Phase I, open-label trial enrolled HER2-negative, CXCR4-positive MBC patients previously treated with 1-3 chemotherapy (CT) regimens for MBC. A 3 + 3 dose escalation design was used, followed by an Expanded Cohort. All cohorts received E on days 2 and 9, and B on days 1-3, and 8-10 of 21-day cycles.
Eleven cohorts were enrolled receiving B at 0.5-5.5 mg/kg. As no DLT was confirmed the MTD was not reached, so the highest B dose (5.5mg/kg) cohort was expanded to 24 pts. In the overall population, median age was 55.5 [33-82] years and median number of prior CT regimens for MBC was 2. TNBC pts were 13 (23%).Most common Gr 3-4 AEs were neutropenia (23 [41%]) and febrile neutropenia (6 [11%]). Two (3.6%) pts died due to septic shock and pneumonia. Anti-tumour activity is summarised in the table. Table: 285PD
|Expanded Cohort||Overall Population|
|(n = 24)||(n = 54)|
|Objective Response Rate, N (% [95% CI])||9 (37·5% [18·8 − 59·4])||16 (29·6% [18·0 − 43·6])|
|Clinical Benefit Rateb, N (% [95% CI])||15 (62·5% [40·6 − 81·2])||24 (44·4% [30·9 − 58·6])|
|Median Treatment Duration (weeks, range)||25·9 (4·4-50·9)||16·0 (1·4-72)|
a. Patients who received at least one full cycle of study treatment. b. CR+PR+SD ≥6 months In the Expanded Cohort, median PFS was 6·2 [95% CI, 2·9–8·1] months and 1 year OS was 75% [95% CI, 53–88]. Mature OS data for the Overall Population and the Expanded Cohort will be presented.
This is the first trial to investigate a CXCR4 antagonist in MBC. The tolerability profile and promising anti-tumor activity observed with B + E in this Phase I study warrants further investigation as well as exploration of additional combinations of B with other anti-cancer therapies.
Clinical trial identification
Legal entity responsible for the study
J. Cortes Castan: Consultancy fees: Polyphor; Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer; Consulting Roche, Celgene, AstraZeneca, Cellestia Biotech, Biothera, Merus. M. Martín: Grant: Novartis; Personal fees: Amgen, Roche, AstraZeneca, Pfizer. S. Pernas Simon: Consultancy and advisory board fees: AstraZeneca, Celgene, Roche. S. Lopez-Tarruella: Consultancy and advisory fees: Celgene, Pfizer, Novartis, AstraZeneca; Travel fees: Roche. L.M. Manso: Research funding: Tesaro. J.A. Perez Fidalgo: Travel fees: Roche, Pfizer, AstraZeneca; Speaker bureau: Roche, Pfizer, AstraZeneca, Ipsen, PharmaMar. C. Hernando: Immediate family member, stocks and employment: Celgene. F. Ademuyiwa: Research funding: Abbvie, Seattle Genetics, Nektar. I.A. Mayer: Advisory board honoraria: Novartis, AstraZeneca, Lilly; Research funding: Pfizer, Genentech. T. Pluard: Personal fees: Novartis, Pfizer, Genentech. M. Martinez Garcia: Consultancy fees: Roche, Celgene; Speaker's bureau: Roche, Pierre Fabre; Travel fees: Roche, Celgene. L.T. Vahdat: Research funding: OTS, Rexahn, Immunomedics, Pharmamar; Honoraria and consultancy fees: Celldex, Seattle Genetics; Speaker's bureau: Eisai. A. Wach, B. Romagnoli: Shareholder and employee: Polyphor. D. Barker: Shareholder: Polyphor and Novartis; Employee: Polyphor. P.A. Kaufman: Consultancy fees: Polyphor, Eisai, Roche/Genentech. All other authors have declared no conflicts of interest.