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Balixafortide (a novel CXCR4 inhibitor) and Eribulin in HER2-neg Metastatic Breast Cancer (MBC) patients (pts): a Phase I trial

Date

21 Oct 2018

Session

Poster Discussion session - Breast cancer, metastatic

Presenters

Javier Cortes Castan

Citation

Annals of Oncology (2018) 29 (suppl_8): viii90-viii121. 10.1093/annonc/mdy272

Authors

J. Cortes Castan1, M. Martín2, S. Pernas Simon3, P. Gomez Pardo4, S. Lopez-Tarruella5, M. Gil Martin3, L.M. Manso6, E.M. Ciruelos7, J.A. Perez Fidalgo8, C. Hernando8, F. Ademuyiwa9, K. Weilbaecher9, I.A. Mayer10, T. Pluard11, M. Martinez Garcia12, L.T. Vahdat13, A. Wach14, D. Barker14, B. Romagnoli14, P.A. Kaufman15

Author affiliations

  • 1 Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 2 Instituto De Investigación Sanitaria Gregorio Marañón, Ciberonc, Geicam, Universidad Complutense, Madrid/ES
  • 3 Departamento De Oncología Médica, Institut Català d’Oncologia L’Hospitalet-Barcelona, - - Barcelona/ES
  • 4 Servicio Oncología Médica, Vall d'Hebron University Hospital, 8035 - Barcelona/ES
  • 5 Instituto De Investigación Sanitaria Gregorio Marañón, Ciberonc, Geicam, Universidad Complutense, - - Madrid/ES
  • 6 Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 7 Medical Oncology  , Hospital Universitario 12 de Octubre, 28041 - Madrid/ES
  • 8 Medical Oncology, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 9 Department Of Hematology And Oncology, Washington University, - - St Louis/US
  • 10 Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, 37232-6838 - Nashville/US
  • 11 Kc School Of Medicine, St Luke’s Cancer Institute, - - Kansas city/US
  • 12 Servicio De Oncología, University Hospital del Mar, 8003 - Barcelona/ES
  • 13 Division Of Hematology & Medical Oncology, Weill Medical college, 10021 - New York/US
  • 14 Clinical Development, Polyphor AG, 4123 - Allschwil/CH
  • 15 Hematology/oncology, Norris Cotton Cancer Center Dartmouth-Hitchcock Medical Center, 3756 - Lebanon/US
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Resources

Background

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.

Methods

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.

Results

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

Efficacy populationa

Expanded CohortOverall 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.

Conclusions

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

NCT01837095.

Legal entity responsible for the study

Polyphor.

Funding

Polyphor.

Editorial Acknowledgement

Disclosure

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.

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