- Evidence
- BSome human evidence
- FDA status
- In clinical trialsas of 2026-10-27
- Route
- Intravenous
- Studies cited
- 2 human0 animal or cell
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.
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 synthetic cyclic peptide designed by Polyphor, a Swiss company, to block CXCR4, a chemokine receptor found on many cancer cells and on blood stem cells. It is given by intravenous infusion. 1
It was studied mainly in HER2-negative metastatic breast cancer in combination with the chemotherapy drug eribulin. The programme reached phase 3 before being abandoned. 12
How it works
CXCR4 is a receptor for the chemokine CXCL12, a signalling protein made in bone marrow, lung, liver and lymph nodes. Cancer cells that carry CXCR4 are drawn toward CXCL12-rich tissues, which helps them spread and shelters them from chemotherapy. Blocking CXCR4 was expected to make tumour cells more exposed to treatment and to interfere with the supportive signals they receive from surrounding tissue. The same receptor is targeted by plerixafor and motixafortide to mobilise stem cells for transplant. 1
What human research shows
A single-arm phase 1 trial published in The Lancet Oncology in 2018 gave balixafortide with eribulin to 56 women with heavily pretreated HER2-negative metastatic breast cancer. The combination produced partial responses in 16 of the 54 patients who could be evaluated (30%), which the investigators saw as promising against historical response rates for eribulin alone. There was no control group. 1
FORTRESS, the randomized, open-label phase 3 trial, enrolled 432 patients to eribulin alone or eribulin plus balixafortide, with response rate and progression-free survival as co-primary endpoints. In June 2021 the primary analysis of response rate in patients treated in the third line or later found 13.0% with the combination versus 13.7% with eribulin alone, and the clinical benefit rate was slightly higher without balixafortide (19.6% versus 16.7%). Polyphor reported in August 2021 that progression-free survival had also not improved and that an interim analysis of overall survival showed no difference, and 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 commonest adverse events were fatigue (79% of patients), neutropenia (low white cell count, 57%), infusion-related reactions (48%), hair loss, constipation and nausea. Serious adverse events occurred in 38% of patients and two died during treatment, one of septic shock and one of pneumonia; the investigators judged the safety profile similar to eribulin alone. FORTRESS did not report new safety signals before closure. Because development stopped, there are no long-term safety data and no reason to expect further study. 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 and compared its response rate with historical figures for eribulin. When FORTRESS randomized 432 patients against a real eribulin control, the response rates were the same (13.0% versus 13.7%). Single-arm results overstating benefit is a common pattern in oncology. 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 carrying it can migrate to and hide in those tissues. Blocking it was meant to expose them to chemotherapy, but that did not translate into clinical benefit in breast cancer. 1
Is balixafortide related to motixafortide?
Both are cyclic peptide CXCR4 antagonists. Motixafortide (Aphexda) is FDA-approved for mobilising stem cells before transplant in multiple myeloma. Balixafortide was developed for cancer treatment and 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