A combination of Polyphor‘s investigational therapy balixafortide (POL6326) and Eisai‘s Halaven (eribulin) may prolong the survival of women with HER2-negative metastatic breast cancer, a Phase 1 trial shows.

The findings were presented in the poster “Balixafortide (a CXCR4 antagonist) + eribulin in HER2-negative metastatic breast cancer (MBC): Survival outcomes of the phase I trial” (abstract #2606) at the recent 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Balixafortide is a potent and selective inhibitor of CXCR4, a protein receptor that controls cancer and immune cell migration, tumor growth, survival, and metastasis (cancer’s spread to other regions or organs). High levels of CXCR4 are normally associated with tumor aggressiveness and a poor prognosis.

According to Polyphor, balixafortide is the only CXCR4 inhibitor currently in development as a combination therapy for breast cancer, and the most advanced CXCR4 blocker for other types of solid tumors.

Halaven is a chemotherapy agent that prevents cancer cells from dividing and proliferating by interfering with internal components called microtubules. It is approved by the U.S. Food and Drug Administration (FDA) to treat people who have already tried other treatments for their metastatic breast cancer.

Balixafortide plus Halaven was evaluated in the open-label, single-arm Phase 1 trial (NCT01837095) that enrolled 56 women with HER2-negative, CXCR4-positive advanced breast cancer. All had previously received up to three different chemotherapy regimens for their cancer.

Participants were divided in different groups and treated with increasing doses of balixafortide (0.5−5.5mg/kg) on days one–three and eight–10, and one of two doses of Halaven (1.4mg/m² or 1.1mg/m²) on days two and nine, in a treatment cycle of 21 days. All continued treatment until disease progression or unacceptable toxicity.

The study’s primary goals included incidence of dose-limiting toxicities; the type, frequency, and severity of adverse events; the establishment of the maximum treatment dose; and pharmacokinetic properties (how a drug is absorbed, distributed, metabolized, and eliminated from the body). Secondary endpoints included patients’ progression-free survival (PFS, the time patients lived without their disease worsening), overall survival (OS), and objective response rate (ORR, the percentage of patients who responded to treatment).

Previous trial data, published in The Lancet Oncology and presented at the European Society for Medical Oncology (ESMO) 2018 Congress, showed that the safety and tolerability profile of the combination therapy was similar to that of Halaven or balixafortide alone.

Of the 54 patients who were eligible to be assessed for effectiveness, 16 (30%) had a partial response (partial tumor eradication) to treatment.

Eisai presented additional trial findings related to survival at 2019 ASCO:

• 50% of patients in the expanded cohort (EC) and 42.4% of the patients from the overall efficacy population (OEP) achieved 18-month survival, receiving the balixafortide-Halaven combo as a second line therapy or later;
• 33.3% of patients from the EC group and 25% in the OEP group achieved 24-month survival, also receiving the balixafortide-Halaven combo as a second line therapy or later;
• 40% of patients from the EC group and 32.5% in the OEP group achieved 18-month survival, receiving the balixafortide-Halaven combo as a third line therapy or later;
• 25% of patients from the EC group and 19% in the OEP group achieved 24-month survival, also receiving the balixafortide-Halaven combo as a third line therapy or later.

Overall, survival data at both time-points were consistent with previous findings from the study.

Treatment safety was also consistent with previous data, with the most common adverse events reported including fatigue (79%), low white blood cell count (57%), infusion-related reactions (48%), constipation (46%), hair loss (46%), and nausea (45%).

“These survival rates, especially for the EC group, are higher than those reported for eribulin [Halaven] monotherapy in similar MBC [ metastatic breast cancer] populations,” the researchers wrote. “These promising results suggest the combo therapy could potentially provide a new treatment option in heavily pre-treated patients with HER2-negative MBC.”

This investigational combo therapy is currently being investigated in a pivotal, randomized Phase 3 trial (NCT03786094) in up to 384 women with HER2-negative, metastatic or locally recurrent breast cancer. The study is currently recruiting participants; more information is available here.

“We are encouraged by the results of this study for patients who received the combination of eribulin  and balixafortide as second line or later therapy for the treatment of HER-2 negative metastatic breast cancer,” David D’Adamo, MD, PhD, senior director of clinical research in Oncology at Eisai, said in a press release.

“With up to 6 percent of new breast cancer cases diagnosed as metastatic, this combination merits further investigation,” he added.

Balixafortide-Halaven as a combo therapy received Fast Track designation by the U.S. Food and Drug Administration in 2018 as third-line therapy for HER2-negative, metastatic breast cancer. This designations supports and helps to speed the treatment’s development and regulatory review, as well as its potential marketing approval.