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FDA Grants Balixafortide Fast Track Designation for Treatment of Metastatic Breast Cancer Subset

Shannon Connelly
Published Online:7:03 PM, Wed April 25, 2018
The immunotherapy agent balixafortide (POL6326) has been granted Fast Track designation by the FDA in combination with eribulin (Halaven) for the treatment of patients with HER2-negative metastatic breast cancer who have previously received at least 2 chemotherapeutic regimens in the metastatic setting, according to Polyphor, the manufacturer of the potent and highly selective CXCR4 antagonist.
The Fast Track program is designed to accelerate the development, review, and approval of drugs that treat serious and life-threatening conditions. As a result of the program, Polyphor will be able to interact with the FDA more often to aid in the expedited development of the agent.

The combination has demonstrated activity in a phase Ib study, which investigated the anti-tumor activity, safety, tolerability, and pharmacokinetics of the addition of balixafortide in patients with metastatic breast cancer with any positive CXCR4 expression level at the tumor site. Overall response rate, progression-free survival, and overall survival were secondary objectives of the trial.

The dose-expansion cohort enrolled 25 patients who had histologically confirmed HER2-negative metastatic breast cancer, were in the second to fourth line of chemotherapy in the metastatic setting, and had evidence of CXCR4 expression. Balixafortide was given at the recommended phase II dose of 5.5 mg/kg on days 2 and 9 and eribulin was given at a dose of 1.4 mg/m2 for the first 3 days and days 8 through 10, based on 21-day cycles. Therapy was discontinued in 1 patient after the first treatment due to rapid disease progression.

The patients had a median age of 59 (range, 33-72). Fifteen patients (60%) had an ECOG performance status of 1, and 10 patients (40%) had an ECOG performance status of 0. Twelve patients (48%) had a tumor receptor status of ER+/PR+/HER2-, 7 patients (28%) had a status of ER+/PR-/HER2-, 2 patients (8%) had a status of ER-/PR+/HER2-, and 4 patients were triple-negative. Eighteen patients (72%) had low CXCR4 expression, 3 patients (12%) had medium CXCR4 expression, and 4 patients (14%) had high CXCR4 expression.

Thirteen of the patients (52%) had 2 prior lines of chemotherapy, 7 patients (28%) had 3 prior lines of chemotherapy, and 5 patients (20%) had 1 prior line of chemotherapy. The majority of patients had metastatic sites most commonly in the liver (76%) and bone (60%), followed by the lung (36%) and lymph nodes (20%).

Among the 24 patients included in the efficacy data calculation, the objective response rate was 38%. Zero patients had a complete response, 9 patients (38%) achieved a partial response, and 7 patients (29%) had meaningful stable disease of 6 months. The clinical benefit rate was 67%.

Fourteen of the 24 patients remained on treatment for 8 cycles or longer. As of the cutoff date of April 11, 2017, 6 patients remain on treatment.

According to lead study investigator Marta Gil-Martin, MD, of Institut Català D'Oncologia, L’Hospitalet de Llobregat, et al, the most common AEs related to balixafortide included histamine-like infusion reactions in 22 patients (88%), which were mostly mild and manageable with anti-histamines and slower infusion rates, and febrile neutropenia in 2 patients (8%).

All of the serious adverse events (SAEs) reported in the trial were related to eribulin alone or in combination with balixafortide. SAEs related to the combination included grade 3 mucosal inflammation and grade 4 neutropenia reported by 1 patient, mild fever of unknown origin in 1 patient who was hospitalized, and grade 4 neutropenia in 1 patient who was diagnosed with pneumonia that responded poorly to antibiotics. The patient received a full treatment schedule for cycle 2 and was hospitalized for severe respiratory distress 5 days after the last treatment. The patient later died of pneumonia.

The most common hematologic AEs of all grades regardless of drug relationship included neutropenia, anemia, thrombocytopenia, and lymphopenia. Non-hematologic AEs of any grade included Infusion-related reaction/histaminergic reaction (88%), asthenia/fatigue (84%), cough (56%), and alopecia (44%).

"We have already identified a development path for balixafortide with input from the FDA to conduct a single pivotal study in this indication. Fast Track designation is another positive step for the development of balixafortide and a recog­nition of the need for better treatments for this group of patients," said Giacomo Di Nepi, Chief Executive Officer of Polyphor.
Gil-Martin M, Pardo PG, Lopez-Tarruella S, et al. Phase Ib Study of the Combination of Balixafortide (a CXCR4 inhibitor) and Eribulin in HER2-Negative Metastatic Breast Cancer Patients. Presented at: 2017 American Society of Clinical Oncology Annual Meeting; Chicago, IL; June 2-6, 2016. Abstract 2555.

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