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DRUG:

balixafortide (POL 6326)

i
Other names: POL 6326, POL6326
Company:
Fosun Pharma, Spexis
Drug class:
CXCR4 antagonist
20d
New trial • Metastases
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CXCR4 (Chemokine (C-X-C motif) receptor 4)
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balixafortide (POL 6326)
1year
FORTRESS: Pivotal Study in HER2 Negative, Locally Recurrent or Metastatic Breast Cancer (clinicaltrials.gov)
P3, N=432, Terminated, Spexis AG | Active, not recruiting --> Terminated; The study was halted early due to failure to meet the primary endpoint.
Trial termination • Combination therapy • Metastases
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Halaven (eribulin mesylate) • balixafortide (POL 6326)
1year
Development of a rare earth nanoprobe enables in vivo real-time detection of sentinel lymph node metastasis of breast cancer using NIR-IIb imaging. (PubMed, Cancer Res)
Of note, the probes accurately detected both macrometastases and micrometastases in SLNs. These results overall underscore the potential of ErNPs@POL6326 for real-time visualization of SLNs and in vivo screening for SLN metastasis.
Preclinical • Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4)
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balixafortide (POL 6326)
over1year
A CXCR4 inhibitor (balixafortide) enhances docetaxel-mediated antitumor activity in a murine model of prostate cancer bone metastasis. (PubMed, Prostate)
Our data demonstrate that a combination of BAL and DOC has greater antitumor activity in a model of PCa bone metastases than either drug alone. These data support further evaluation of this combination in metastatic PCa.
Preclinical • Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4) • IFNG (Interferon, gamma) • CD34 (CD34 molecule) • CASP3 (Caspase 3)
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CD34 positive
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paclitaxel • docetaxel • balixafortide (POL 6326)
over1year
Balixafortide, a CXCR4 inhibitor, synergizes with docetaxel to diminish tumor growth in a prostate cancer model of bone metastasis. (AUA 2023)
Our data demonstrate that that a combination of BLX and DOC has greater anti-tumor activity in a model of PCa bone metastases than either drug alone. The anti-tumor activity was also associated with decreased tumor-induced bone lesions. The mechanism for the anti-tumor activity is not completely elucidated at this time but does not appear to be through impacting proliferation.
Preclinical
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CXCR4 (Chemokine (C-X-C motif) receptor 4) • IFNG (Interferon, gamma) • CD34 (CD34 molecule) • CASP3 (Caspase 3)
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CD34 positive
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docetaxel • balixafortide (POL 6326)
almost2years
Enrollment change • Trial withdrawal • Combination therapy • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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HER-2 negative
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albumin-bound paclitaxel • Halaven (eribulin mesylate) • balixafortide (POL 6326)
3years
Balixafortide (a CXCR4 antagonist)+eribulin versus eribulin alone in patients with HER2 negative, locally recurrent or metastatic breast cancer: An international, randomized, phase 3 trial (FORTRESS) (SABCS 2021)
In this Phase 3 randomized trial, no differences in ORR, CBR, mPFS, or mOS were observed for B + E compared to E alone in any population of HER2‑mBC patients. Efficacy parameters for E alone were similar to those reported previously. The combination was B + E was well-tolerated overall.
Clinical • P3 data
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 negative
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Halaven (eribulin mesylate) • balixafortide (POL 6326)
over3years
Macrocycle Therapeutics to Treat Life-threatening Diseases. (PubMed, Chimia (Aarau))
Furthermore, POL6014, an inhibitor of neutrophile elastase and balixafortide, a CXCR4 inhibitor have been discovered and developed from the platform. Currently a combination of balixafortide and eribulin is in Phase III clinical trial for the treatment of patients with advanced metastatic HER2-negative breast cancer.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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HER-2 negative
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Halaven (eribulin mesylate) • balixafortide (POL 6326)
over3years
New P1/2 trial
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 negative
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albumin-bound paclitaxel • Halaven (eribulin mesylate) • balixafortide (POL 6326)
almost4years
[VIRTUAL] Efficacy of Balixafortide (POL6326) and Paclitaxel alone and in combination in humanized breast cancer PDX (AACR 2021)
Balixafortide (POL6326) is a potent, selective inhibitor of the chemokine receptor CXCR4 in PhIII for metastatic HER2-negative breast cancer (BC) in combination with tubulin-binding eribulin (NCT03786094). There was no decrease in tolerability in balixafortide combination vs paclitaxel alone. This data suggests combination with balixafortide is more efficacious and equally tolerated to paclitaxel single agent treatment.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • CD34 (CD34 molecule)
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HER-2 negative
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paclitaxel • Halaven (eribulin mesylate) • balixafortide (POL 6326)
4years
At the bedside: Profiling and treating patients with CXCR4-expressing cancers. (PubMed, J Leukoc Biol)
To date, Sanofi Genzyme's plerixafor is the only marketed CXCR4 inhibitor (i.e., Food and Drug Administration-approved in 2008 for stem cell mobilization)...These small molecules, peptides, and Abs include balixafortide (POL6326, Polyphor), mavorixafor (X4P-001, X4 Pharmaceuticals), motixafortide (BL-8040, BioLineRx), LY2510924 (Eli Lilly), and ulocuplumab (Bristol-Myers Squibb)...Biol. xx: xx-xx; 2020.
Clinical • Review • Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL12 (C-X-C Motif Chemokine Ligand 12)
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Xolremdi (mavorixafor) • balixafortide (POL 6326) • LY2510924 • ulocuplumab (BMS-936564) • Aphexda (motixafortide) • plerixafor
4years
[VIRTUAL] Balixafortide (a CXCR4 antagonist) plus eribulin in HER2 negative metastatic breast cancer: Final analysis from the Phase 1 single arm trial (SABCS 2020)
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 endpoints 2, 3 . The safety and tolerability of B + E appear comparable to published data on E or B alone, particularly for neutropenia and peripheral neuropathy 1 .
P1 data
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HER-2 (Human epidermal growth factor receptor 2) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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HR positive • HER-2 negative • CXCR4 positive
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Halaven (eribulin mesylate) • balixafortide (POL 6326)
over4years
Relevance of the CXCR4/CXCR7-CXCL12 axis and its effect in pathophysiological conditions. (PubMed, Pharmacol Res)
It is therefore of great interest to investigate CXCR4/CXCR7/CXCL12 modulators in clinical development, with several CXCR4 and CXCL12 modulators such as plerixafor, ulocuplumab, balixafortide, and olaptesed pegol having already reached this stage...Contrary to CXCR4 and CXCL12 modulators, CXCR7 modulators have, thus far, not been extensively studied. Therefore, more (pre)clinical investigations are needed.
Review • Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4)
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doxorubicin hydrochloride • Xtandi (enzalutamide) • balixafortide (POL 6326) • olaptesed pegol (NOX-A12) • LY2510924 • ulocuplumab (BMS-936564) • Aphexda (motixafortide) • plerixafor
over4years
Clinical • P3 data
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 negative
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Halaven (eribulin mesylate) • balixafortide (POL 6326)
over4years
[VIRTUAL] Balixafortide (a CXCR4 antagonist) plus eribulin in HER2 negative metastatic breast cancer: Dose-response analysis of efficacy from phase I single-arm trial. (ASCO 2020)
A consistent dose response effect for B + E was suggested in heavily pretreated pts with HER2 negative MBC across all efficacy endpoints. A comparison of these efficacy results, and particularly response data, with single agent data for E in similar populations2, 3 showed that pts in the EC had a more profound benefit observed consistently throughout all efficacy endpoints. Further data and analysis will be forthcoming for presentation.
Clinical • P1 data
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HER-2 (Human epidermal growth factor receptor 2) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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HR positive • HER-2 negative • HR positive + HER-2 negative
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Halaven (eribulin mesylate) • balixafortide (POL 6326)
almost5years
Clinical significance of chemokine receptor antagonists. (PubMed, Expert Opin Drug Metab Toxicol)
This study will provide an overview of approved chemokine receptor antagonists and promising candidates in advanced clinical trials.Areas covered: We will describe clinical aspects of chemokine receptor antagonists regarding their clinical efficacy, mechanisms of action, and re-purposed applications.Expert opinion: Three chemokine antagonists have been approved: (i) plerixafor is a small-molecule CXCR4 antagonist that mobilizes hematopoietic stem cells; (ii) maraviroc is a small-molecule CCR5 antagonist for anti-HIV treatment; and (iii) mogamulizumab is a monoclonal-antibody CCR4 antagonist for the treatment of mycosis fungoides or Sézary syndrome. Moreover, phase 3 trials are ongoing to evaluate many potent candidates, including CCR5 antagonists (e.g. leronlimab), dual CCR2/CCR5 antagonists (e.g. cenicriviroc), and CXCR4 antagonists (e.g. balixafortide, mavorixafor, motixafortide). The success of chemokine receptor antagonists depends on the selective blockage of disease-relevant chemokine receptors which are indispensable for disease progression. Although clinical translation has been slow, antagonists targeting chemokine receptors with multifaced functions offer the potential to treat a broad spectrum of human diseases.
Clinical • Review • Journal
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CXCR4 (Chemokine (C-X-C motif) receptor 4)
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Poteligeo (mogamulizumab-kpkc) • Xolremdi (mavorixafor) • balixafortide (POL 6326) • Selzentry (maraviroc) • Vyrologix (leronlimab) • Aphexda (motixafortide) • plerixafor
5years
Clinical • P3 data
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HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
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Halaven (eribulin mesylate) • balixafortide (POL 6326)