Peptide education
Balixafortide
POL6326
Balixafortide is an investigational peptide that blocks CXCR4. It has been studied by intravenous infusion with eribulin in people with HER2-negative advanced breast cancer.
Balixafortide remains investigational in the United States. An early response signal cannot outweigh the negative randomized comparison for the endpoint studied.
Overview
Quick answer
The early study used the combination without a control group. The later randomized FORTRESS comparison did not show a progression-free survival advantage from adding balixafortide to eribulin.
Is balixafortide FDA-approved?
Exact openFDA active-ingredient and brand-name searches found no matches for balixafortide or POL6326. Other names and jurisdictions require separate checks.
What happened in the early trial?
Sixteen of 54 evaluable participants had a partial response during treatment with balixafortide plus eribulin. With no control group, the response cannot be assigned to balixafortide alone.
What did FORTRESS find?
The registry reports median progression-free survival of 3.5 months for the combination versus 4.0 months for eribulin alone in the overall population. In a separate third-line-or-later analysis of 330 patients, an investigator conference abstract reported independently assessed objective response rates of 13.0% versus 13.7%. Both were primary efficacy measures; the trial stopped early after its primary endpoints were not met.
Evidence
Evidence snapshot
Partial responses occurred during combination treatment in an uncontrolled phase 1 study.
The phase 3 registry reports no demonstrated improvement in progression-free survival for the combination over eribulin alone.
The early study reported fatigue, neutropenia, and infusion reactions, as well as serious adverse events.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Early responses establish that balixafortide adds benefit to eribulin. | The phase 1 study had no eribulin-only group. The later randomized trial did not meet its progression-free survival or objective response efficacy endpoints. | The early response rate does not establish added benefit. |
| FORTRESS proves balixafortide can never work in any setting. | The randomized result applies to the studied treatment combination, population, and endpoints. The trial stopped early. | The trial did not show a benefit in that comparison; it cannot settle every possible population or treatment combination. |
Bottom line
Main takeaway
Balixafortide is not an established breast cancer treatment.
A response in an uncontrolled combination study is different from improvement over eribulin alone.
The phase 3 figures come from registry results and a conference abstract, not a full trial report.
Identity
What it is
Balixafortide, also called POL6326, is a cyclic CXCR4 antagonist. Both it and eribulin were administered intravenously in the phase 1 breast cancer trial.
Research
Research evidence
The phase 1 combination study and the randomized FORTRESS trial answer different questions. The latter directly compared the combination with eribulin alone.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Phase 1 combination study | 56 previously treated women with HER2-negative metastatic breast cancer | Single-arm dose escalation with expansion | Intravenous balixafortide plus eribulin | 16 of 54 evaluable participants had a partial response. | No control group; both medicines were given together. | Early uncontrolled human evidence |
| FORTRESS NCT03786094: Pivotal study in HER2 negative, locally recurrent or metastatic breast cancerNCT03786094: Balixafortide plus eribulin versus eribulin alone in HER2-negative locally recurrent or metastatic breast cancer: FORTRESSNCT03786094: Polyphor provides update on the phase 3 FORTRESS study of balixafortide | 432 patients with HER2-negative locally recurrent or metastatic breast cancer | Randomized, open-label phase 3 trial | Balixafortide plus eribulin versus eribulin alone | Overall-population median progression-free survival was 3.5 versus 4.0 months in registry-posted results. A conference abstract reported independently assessed objective response rates of 13.0% versus 13.7% in a separate analysis of 330 patients receiving third-line or later treatment. | Stopped early; the registry results and conference abstract are not a full journal report. The response and progression-free survival figures use different analysis populations. | Randomized comparison, primary efficacy endpoints not met |
Use context
Reported use context
Trial dosing was administered in oncology research and is not a recommendation.
Study and label context
Balixafortide 5.5 mg/kg on days 1 to 3 and 8 to 10 of a 21-day cycle, with eribulin given on days 2 and 9.
Study-reported only, not a recommendation or an approved regimen.Cautions
Safety and unknowns
- In the phase 1 combination study, common events included fatigue, neutropenia, and infusion reactions. Serious adverse events occurred, and two participants died while receiving study treatment. A treatment-related fatal adverse event prompted a protocol amendment.
- Because eribulin was given with balixafortide, the uncontrolled study cannot attribute every adverse event to one medicine.
Product quality
Product identity and quality
Study results apply to controlled research material and do not verify the identity, purity, or sterility of an unrelated product.
Approval status
The exact-name FDA search covered balixafortide and POL6326, not every name or jurisdiction.
Mechanism
How it is proposed to work
Balixafortide blocks CXCR4, a receptor involved in cell movement and signaling.
The CXCR4 and CXCL12 pathway was part of the rationale for combining this compound with chemotherapy. A mechanism is not proof of an improvement in patient outcomes.
FAQ
Common questions
Did adding balixafortide improve progression-free survival?
The FORTRESS registry reports no demonstrated improvement in its randomized comparison with eribulin alone.
Details
Technical details
Sources
References
- 1.
doi:10.1016/S1470-2045(18)30147-5 PMID:29706375 NCT01837095
Single-arm combination trial; responses cannot be attributed to balixafortide alone.
- 2.
ClinicalTrials.gov. Pivotal study in HER2 negative, locally recurrent or metastatic breast cancer
NCT03786094
Registry-posted phase 3 results and termination reason; not a peer-reviewed full trial report.
- 3.
Cancer Research conference abstract. Balixafortide plus eribulin versus eribulin alone in HER2-negative locally recurrent or metastatic breast cancer: FORTRESS
doi:10.1158/1538-7445.SABCS21-PD13-01 NCT03786094
Investigator conference abstract reports objective response in 330 patients in the third-line-or-later analysis; it is not a full trial report.
- 4.
Study sponsor. Polyphor provides update on the phase 3 FORTRESS study of balixafortide
NCT03786094
Sponsor announcement reports the initial objective response analysis; it is not a full independent trial report.
- 5.
FDA. Drugs@FDA approved drug products database
Search balixafortide and POL6326 in Drugs@FDA. This link opens the search page, not a saved result.
- 6.
FDA. FDA information about Drugs@FDA coverage
Exact openFDA active-ingredient and brand-name queries for balixafortide and POL6326 found no matches. This page describes database coverage, not the saved results; other names and jurisdictions are not assessed.