Angiochem, a clinical stage biotechnology company developing drugs that are uniquely capable of crossing the blood-brain barrier (BBB), announced that the complete analysis results of a Phase 2 clinical study with ANG1005, a novel paclitaxel-peptide drug conjugate, in breast cancer patients with brain metastasis were presented today at the 2013 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference. These data, which include the complete intent-to-treat (ITT) analysis, demonstrated promising signs of anti-tumor activity, and support the company's decision to advance the ANG1005 clinical development program.
Angiochem presented the Phase 2 ITT analysis with ANG1005 in 80 HER2-positive and HER2-negative breast cancer patients with brain metastases. Two doses, 650mg/m2 (n=13) and 550mg/m2 (n=67), were evaluated for intracranial anti-tumor responses including response rate, progression-free survival (PFS) and overall survival (OS) as well as safety and tolerability.
In the study, ANG1005 was generally safe and well-tolerated, and demonstrated an adverse event profile consistent with conventional taxane therapy in both HER2-positive and HER2-negative cohorts at both dose levels studied. In addition, patients in both the HER2-positive and HER2-negative populations experienced anti-tumor responses including up to 14 patients with intracranial partial responses (PR), 35 patients with stable disease (SD) and six months overall survival in up to 85%.
"Based on these encouraging results, we are excited to advance ANG1005 into further clinical development," said Jean-Paul Castaigne, MD, CEO of Angiochem. "We believe that ANG1005 can bring significant benefit to patients with brain metastases and primary brain cancer diseases with significant unmet medical need due to the inability of most anti-cancer agents to cross the blood-brain barrier."
In a poster presentation entitled "A phase II study of ANG1005, a novel, brain-penetrant taxane derivative, in breast cancer patients with brain metastases," Nancy U. Lin, Dana-Farber Cancer Institute, and co-authors presented complete Phase 2 ITT final analysis data with ANG1005, confirming previously reported Phase 1 observations in which safety, tolerability and early signs of efficacy in brain metastases were demonstrated.
ANG1005 was generally safe and well-tolerated with taxane-related adverse events including neutropenia, fatigue, peripheral neuropathy and mucosal inflammation. HER2-positive patientss (9, 25%) and SD (18, 50%) thereby demonstrating disease control in 75% of those patients. In addition, at the dose level of 550 mg/m2, three month PFS was 71% with a median PFS of 128 days and OS at six months of 82%.
Her2-negative patientss (5, 11%) and SD (17, 32%) thereby demonstrating disease control in 50% of those patients. In addition, at the dose level of 550 mg/m2, three months of PFS was 35% with a median PFS of 84 days and OS at six months of 60%.
Based on these results, Angiochem will advance ANG1005 into further clinical development including a Phase 2 clinical study in patients with recurrent high grade gliomas which began enrolling in October 2013 and a Phase 2 clinical study in HER2-positive breast cancer patients with brain metastases which will begin enrolling in the first quarter of 2014.