- Evidence
- BSome human evidence
- FDA status
- In clinical trialsas of 2026-10-27
- Route
- Intravenous
- Studies cited
- 2 human0 animal or cell
A drug meant to make chemotherapy work better in breast cancer. Early results looked good, but a trial of 432 women found no benefit, and work on it stopped.
Sold for
Balixafortide was pitched as a drug that would stop breast cancer cells hiding in protective niches by blocking the CXCR4 receptor, making chemotherapy work better.
Studies say
An encouraging uncontrolled early trial was followed by a 432-patient randomized trial that showed no benefit when balixafortide was added to eribulin (grade B, negative).
Why grade B. A 56-patient single-arm phase 1 trial with eribulin in metastatic breast cancer suggested a higher response rate than eribulin alone, but the randomized phase 3 FORTRESS trial in 432 patients found no improvement in response rate, progression-free survival or overall survival. A negative randomized trial is grade B evidence against the claimed benefit. 123
FDA. Balixafortide is an investigational peptide developed by Polyphor and is not approved by the FDA or any other regulator. Its phase 3 trial in breast cancer (FORTRESS) failed in 2021 and the sponsor closed the study without seeking approval. The only trial registered since then is an investigator-led phase 1 study combining it with cosibelimab in metastatic pancreatic cancer, posted in 2025 and not yet recruiting at its last update.
Written from 3 cited sources. Fact-checked 2026-10-27: 14 claims checked, 4 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Making chemotherapy work better in breast cancer.
- Can a US doctor prescribe it?
- No. It is not approved, and development has stopped.
- Properly tested in people?
- Partly: some human trials, with gaps: a 56-patient early study looked hopeful, then a 432-patient trial found no benefit.
Evidence checklist
- Randomised controlled trial FORTRESS phase 3, eribulin with or without ityes
- Human study over 100 people FORTRESS 432 patientsyes
- More than one research group Sponsor trials only; one programno
- Clinical outcomes, not surrogate markers Response, progression-free and overall survivalyes
- Human safety data beyond case reports Phase 1 and phase 3 adverse event datayes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Balixafortide (POL6326) is a lab-made cyclic peptide. Polyphor, a Swiss company, designed it to block CXCR4. This chemokine receptor sits on many cancer cells and on blood stem cells. Doctors give the drug by intravenous infusion. 1
It was studied mainly in HER2-negative metastatic breast cancer. It was given with the chemotherapy drug eribulin. The programme reached phase 3 and was then dropped. 12
How it works
CXCR4 is a receptor for the chemokine CXCL12. CXCL12 is a signalling protein made in bone marrow, lung, liver and lymph nodes. Cancer cells with CXCR4 are drawn toward tissues rich in CXCL12. This helps them spread. It also shields them from chemotherapy. Blocking CXCR4 was expected to leave tumour cells more open to treatment. It was also expected to cut the support signals they get from nearby tissue. Plerixafor and motixafortide hit the same receptor. They are used to move stem cells into the blood for transplant. 1
What human research shows
A phase 1 trial with a single arm was published in The Lancet Oncology in 2018. Researchers gave balixafortide with eribulin to 56 women. All had HER2-negative metastatic breast cancer and had already had heavy treatment. Of 54 patients who could be evaluated, 16 had partial responses (30%). The investigators saw this as promising against past response rates for eribulin alone. There was no control group. 1
FORTRESS was the phase 3 trial. It was randomized and open-label. It enrolled 432 patients. They got eribulin alone or eribulin plus balixafortide. Response rate and progression-free survival were the two main measures. In June 2021 the main analysis looked at response rate in patients on third-line treatment or later. It found 13.0% with the combination and 13.7% with eribulin alone. The clinical benefit rate was slightly higher without balixafortide (19.6% versus 16.7%). Polyphor reported in August 2021 that progression-free survival had not improved either. An interim analysis of overall survival showed no difference. The study was closed. 23
| Study | Model | Finding |
|---|---|---|
| Pernas 2018, Lancet Oncology (phase 1) | Humans, n=56 women with HER2-negative metastatic breast cancer, single-arm dose-escalation with eribulin | Partial responses in 16 of 54 evaluable patients (30%), with no control arm. 1 |
| FORTRESS phase 3, 2021 | Humans, n=432, randomized, eribulin with or without balixafortide | Response rate 13.0% versus 13.7% in the third-line and later group; clinical benefit rate slightly favoured eribulin alone; progression-free survival also failed and the study closed. 3 |
Safety
In the phase 1 trial, the most common adverse events were fatigue (79% of patients) and neutropenia, a low white cell count (57%). Infusion-related reactions followed (48%). Hair loss, constipation and nausea were also common. Serious adverse events hit 38% of patients. Two died during treatment, one of septic shock and one of pneumonia. The investigators judged the safety profile similar to eribulin alone. FORTRESS reported no new safety signals before it closed. Development has stopped. So there are no long-term safety data, and none are expected. 12
Questions for your clinician
- Is balixafortide available outside a trial, given development stopped?
- What other options exist for my metastatic breast cancer?
- What did the failed phase 3 trial show about benefit?
Questions people ask
Is balixafortide FDA-approved?
No. It failed its phase 3 trial in 2021, and Polyphor stopped developing it. It has not been approved anywhere. 2
Why did the phase 3 trial fail when the phase 1 looked good?
The phase 1 trial had no control group. It compared its response rate with past figures for eribulin. FORTRESS randomized 432 patients against a real eribulin control. The response rates were the same (13.0% versus 13.7%). Single-arm results often overstate benefit in cancer research. 123
What does CXCR4 do in cancer?
It is a receptor that draws cells toward tissues rich in the chemokine CXCL12, such as bone marrow and lung. Tumour cells with it can move into those tissues and hide there. Blocking it was meant to expose them to chemotherapy. That did not lead to clinical benefit in breast cancer. 1
Is balixafortide related to motixafortide?
Both are cyclic peptides that block CXCR4. Motixafortide (Aphexda) is FDA-approved to move stem cells into the blood before transplant in multiple myeloma. Balixafortide was made to treat cancer, and it failed. 1
Citations
- Pernas 2018, Lancet Oncology: balixafortide plus eribulin in HER2-negative metastatic breast cancer, phase 1 trial pubmed.ncbi.nlm.nih.gov
- Clinical Trials Arena: Polyphor's balixafortide fails phase 3 FORTRESS breast cancer study clinicaltrialsarena.com
- OncLive, June 2021: balixafortide plus eribulin fails to improve response rate in the FORTRESS trial onclive.com