The proposed study is intended to support the global registration of balixafortide. Polyphor expects to enroll the first patient in the second quarter of 2019.
Polyphor announced today that it has received the meeting minutes from a Type B Guidance meeting with the US FDA on the study design and statistical analysis plan of the planned Phase III study POL6326-009, that will evaluate the efficacy and safety of balixafortide and eribulin versus eribulin monotherapy in patients with locally recurrent and/or metastatic breast cancer (MBC).
The FDA reviewed the design, inclusion and exclusion criteria of the international, multicenter, randomized, open-label Phase III trial which will comprise a total of 384 patients with HER2 negative MBC, of which 320 patients receiving third line and 64 patients receiving second line chemotherapy. The FDA agreed with the proposed indication for the treatment of MBC in patients who have previously received at least two chemotherapeutic regimens and confirmed the possibility to submit a filing for accelerated approval at the end of the recruitment on the basis of the analysis of the overall response rate (ORR), confirmed by an independent blinded review, and of the associated durability of response. The full approval will be based on the magnitude of Progression Free Survival (PFS) on blinded independent review, supported by an overall survival trend favoring balixafortide arm and a favorable risk-benefit profile.
"This FDA meeting was an important milestone to advance the development of balixafortide and potentially bringing it to the patients suffering from metastatic breast cancer, who have only limited treatment alternatives. We are excited by the opportunity to start the trial in the first quarter of 2019 and have the first patient enrolled by Q2/19," said Giacomo Di Nepi, Chief Executive Officer of Polyphor.
About Balixafortide (POL6326)
Balixafortide is a potent and highly selective antagonist of CXCR4, a G-protein coupled receptor (GPCR) that regulates the trafficking and homing of both cancer cells and cells of the patient's immune system. CXCR4 plays a critical role in tumor growth, survival, angiogenesis and metastasis*. High CXCR4 levels have been detected in almost all human tumor types, including breast cancer. High CXCR4 expression is known to correlate with aggressive metastatic behavior of cancer cells and a poor prognosis**.
Balixafortide is being developed to improve therapy outcomes in cancer, when used in combination with other agents. Balixafortide is the only CXCR4 antagonist in development for breast cancer and is the most advanced CXCR4 antagonist, being developed in solid tumors, being the first product candidate to reach proof of concept. The molecule was discovered based on Polyphor's proprietary macrocycle technology platform. Balixafortide showed strong results in a Phase Ib/proof of concept clinical trial in combination with eribulin in patients affected with advanced metastatic breast cancer. The development path identified with the input of the FDA is to conduct a single pivotal study to achieve approval in HER-2 negative metastatic breast cancer patients who previously received at least two chemotherapeutic regimens in the metastatic setting. Additionally, there is the possibility of achieving an accelerated approval based on interim results. Polyphor is also conducting preclinical work to establish the potential for balixafortide in combination with other drugs and in other oncology indications.
* Otsuka S, Bebb G. J Thorac Oncol. 2008;3(12):1379-1383
** Chatterjee S, Behnam Azad B, Nimmagadda S. Adv Cancer Res. 2014; 124:31-82