Abstract 359TiP
Background
Balixafortide (B), a synthetic cyclic peptide, is a potent selective CXCR4 antagonist with a demonstrated high affinity for the human CXCR4 receptor in in vitro receptor binding studies. Disrupting CXCR4-dependent pathways may prevent development of breast cancer metastases, enhance cytotoxic effects of chemotherapy and immunotherapy, and counteract tumor cell evasion. Encouraging safety/efficacy data were published from a phase I trial investigating B + eribulin (E) in ≥2nd line patients with HER2-negative metastatic breast cancer (mBC)1: Table: 359TiP
| Expansion Cohort (N=24) | Overall Efficacy Population (N=54) | |
| Objective response rate (ORR) | 37.5% | 29.6% |
| Median progression free survival (PFS) (months) | 6.2 | 4.5 |
| Median overall survival (OS) (months) | 18 | 16.8 |
Consequently, a phase III registration trial is ongoing.
Trial design
International, multicenter, open-label, 2-arm trial. Patients are randomized in a 1:1 ratio to B + E or E alone. Eligible patients are aged ≥18 years; have mBC or unresectable locoregionally recurrent BC; histologically confirmed HER2-negative; and have previously received 1−4 chemotherapy regimens in the metastatic setting. Patients with ER+ and/or PgR+ disease must have received at least 1 line of endocrine therapy and be unsuitable for further endocrine therapy. Efficacy endpoints for the overall and ≥3rd line populations are PFS (primary) and OS (key secondary). ORR is a co-primary endpoint for the ≥3rd line population. The design allows for statistical success by meeting at least 1 efficacy endpoint (ORR, PFS or OS) in the ≥3rd line population or at least 1 (PFS or OS) in the overall (≥2nd line population), as prospectively defined considering the locally-approved eribulin label. Patients will be stratified according to: • Lines of chemotherapy (2nd vs. ≥3rd line) • Hormone receptor status • Previous CDK4/6 inhibitor treatment • Visceral vs. non-visceral disease on 22 April 2020, 259 patients from an accrual target of 384 were enrolled in 13 countries. Enrollment is open with completion anticipated by September 2020. 1. Pernas S et al. Lancet Oncol. 2018; 19: 812−24.
Clinical trial identification
NCT03786094.
Editorial acknowledgement
Linda Summerton; tranScrip Stacey Maxwell; tranScrip.
Legal entity responsible for the study
Polyphor Ltd.
Funding
Polyphor Ltd.
Disclosure
P.A. Kaufman: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Polyphor, Lilly, Macrogenics, Eisai, Sanofi, Pfizer; Travel/Accommodation/Expenses: Polyphor, Lilly, Macrogenics. M. Martin: Research grant/Funding (institution): Roche, PUMA, Novartis; Advisory/Consultancy: AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology, Daiichi Sankyo, Pfizer; Honoraria (institution): AstraZeneca, Amgen, Roche/Genentech, Novartis, Pfizer. I. Mayer: Research grant/Funding (institution): Genentech, Pfizer, Novartis; Advisory/Consultancy: Genentech, Pfizer, Novartis, Lilly, AstraZeneca, GSK, Puma, AbbVie, Macrogenics, Immunomedics, Seattle Genetics. L.T. Vahdat: Advisory/Consultancy: Polyphor Ltd; Advisory/Consultancy: Berg Pharma; Advisory/Consultancy: Osmol Therapeutics; Research grant/Funding (institution): Roche, Novartis, Genetech, ARvinas, OTS biosciences ; Honoraria (self): Eisai. S. Pernas Simon: Advisory/Consultancy: Roche, Novartis, Polyphor; Travel/Accommodation/Expenses: Roche, Novartis. P. Schmid: Advisory/Consultancy: Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, Puma; Research grant/Funding (institution): Roche, Genentech, Oncogenex, Novartis; Spouse/Financial dependant: Genentech, Roche. H.L. McArthur: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Travel/Accommodation/Expenses: Genomic Health; Advisory/Consultancy, Travel/Accommodation/Expenses: Immunomedics; Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Research grant/Funding (institution): Ziopharm Oncology; Travel/Accommodation/Expenses: Spectrum Pharmaceuticals; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: DAVA Pharmaceuticals . R. Dent: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca, Merck, Pfizer, Roche; Honoraria (self): Eisai, Novartis, Lilly. H.S. Rugo: Research grant/Funding (institution), Clinical trials through UCSF: Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Seattle Genetics, Eisai, Macrogenics, and Immunomedics: University of California Helen Diller Family Comprehensive Cancer Center; Advisory/Consultancy, Travel/Accommodation/Expenses, Travel support from: Daiichi, Mylan, Pfizer, Merck, AstraZeneca, Novartis and Macrogenics. Limited consulting with Puma and Samsung: University of California Helen Diller Family Comprehensive Cancer Center. C. Barrios: Honoraria (institution), Research grant/Funding (institution): AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Celgene, Covance, Lilly, Medivation, Merck Serono, Merck Sharp Dohme (MSD), Novartis, Pfizer, PharmaMar, Roche/Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, MSD, AstraZeneca, Bayer. A. Bobirca: Full/Part-time employment: Polyphor Ltd. F. Ringeisen: Full/Part-time employment: Polyphor Ltd. J. Cortés: Advisory/Consultancy: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim; Honoraria (institution): Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; Research grant/Funding (institution): Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Shareholder/Stockholder/Stock options: MedSIR; Travel/Accommodation/Expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo.