Balixafortide and Eribulin Shows Modest Responses in Patients with HER2-Negative Breast Cancer

Balixafortide (POL6326) in combination with eribulin (Halaven) did not improve objective response rate (ORR) compared to eribulin alone for the treatment of HER2-negative, locally recurrent or metastatic breast cancer, missing the coprimary end point of the FORTRESS study (NCT03786094), according to a press release by Polyphor AG.¹

Balixafortide is a selective antagonist of the chemokine receptor CXCR4. CXCR4 is a G-protein coupled receptor that regulates both canner and immune system cells.

The randomized, parallel assignment, open-label FORTRESS study has an estimated enrollment of 384 participants and an estimated completion date of March 2022. The other primary end point of the study is progression-free survival (PFS), and the secondary end point was overall survival (OS). Patients in the study were randomized 1:1 to receive either eribulin alone or the combination of balixafortide and eribulin.^1,2

In total, the study randomized 432 patients, and patients were stratified by lines of chemotherapy, hormone receptor status, prior CDK4/6 inhibitor treatment, and whether they had visceral versus non-visceral disease.At least 344 of those patients were on their third or subsequent line of therapy, with 88 patients receiving their second line of chemotherapy. The ORR of the combination was 13%, compared with 13.7% for eribulin alone (P =1.00). In the third line and later cohort, the 6-month duration of response was 16.7% in the combination arm and 19.6% in the monotherapy alone.

The safety and tolerability data of the combination was consistent with prior studies.¹

“Given the high unmet medical need for patients with HER2-negative breast cancer in a late stage of the disease, we are disappointed that the FORTRESS study did not meet its coprimary endpoint,” said Gökhan Batur, chief executive officer of Polyphor, in a press release. “We thank all the patients, investigators, and healthcare professionals as well as our employees for their active participation in this study.”

In order to participate, patients must be 18 years of age and older, have histologically confirmed breast cancer, metastatic breast cancer, be refractory to the most recent chemotherapy with documented progression within 6 months of therapy, have a least 14 days between the start of the study and completion of any previous cancer therapies, have adequate organ function, and have a life expectancy of at least 3 months. Patients who were previously treated with eribulin, have grade 3 or higher peripheral neuropathy, have previously received CXCR4 therapy, are breast feeding or pregnant, or who have congestive heart failure are not eligible to participate.

The combination of balixafortide and eribulin was previously granted a fast track designation for the treatment of HER2-negative metastatic breast cancer in patients who have received at least 2 prior lines of chemotherapy in the metastatic setting by the FDA in 2018.

The fast track designation was based on results of a phase 1b dose-expansion study of the agent which enrolled 25 patients. The median age of the patients was 59. Sixty percent of patients had an ECOG performance status of 0. Additionally, 52% of patients had 2 prior lines of therapy, 28% had 3 prior lines of therapy, and 20% of patients had 1 prior line of therapy. Other metastatic sites included the liver (76%), bone (60%), and lung (36%).

The ORR for this study was 38%. Of those who responded, 38% exhibited a partial response. No complete response was seen. Additionally, 29% had meaningful stable disease for 6 months and the overall clinical benefit rate was 67%.

The future of the current study will be decided in mid-July as the data is analyzed further. 

_REFERENCE:

_{1 Polyphor provides update on the phase III FORTRESS Study of balixafortide in patients with advanced HER2 negative breast cancer. News release. Polyphor AG. June 28, 2021. Accessed June 29, 2021. https://bit.ly/3qBaisw.}

_{2 Kaufman PA, Martin M, Mayer I, et al. 359TiP International phase III trial: Balixafortide (a CXCR4 antagonist) + eribulin versus eribulin alone in patients with HER2-negative, locally recurrent or metastatic breast cancer (FORTRESS). 2020;31(suppl 4):S394-S395. doi: 10.1016/j.annonc.2020.08.461}