BMET-23ANG1005, A NOVEL BRAIN-PENETRANT PEPTIDE-TAXANE CONJUGATE, FOR THE TREATMENT OF CNS METASTASES FROM BREAST CANCER

Abstract

BACKGROUND: Treatment options for brain metastases are limited due to the inability of most anti-cancer agents to cross the blood brain barrier (BBB). ANG1005 is a novel peptide-taxane conjugate, being developed for targeted treatment of brain metastases. It consists of 3 paclitaxel molecules covalently linked to Angiopep-2 designed to cross the BBB and to penetrate malignant cells via the LDL receptor related protein-1 (LRP-1) transport system. METHODS: Adult patients with measurable recurrent brain metastases from breast cancer with, or without, leptomeningeal disease are being enrolled in this multi-center, open-label study, for up to 56 patients. ANG1005 is administered IV at 600 mg/m2 q21d (one cycle). HER2+ patients are allowed to continue HER2 targeted therapies. The primary endpoint is intracranial objective response rate, as per CNS RECIST v.1.1. An imaging sub-study, comparing 18F-FLT-PET to MRI, is also ongoing in 10 patients with brain metastases from breast cancer. RESULTS: Accrual is ongoing and to date, 48 patients have been treated with a range of 1-18 cycles of ANG1005. Median age is 47 years (range: 26-65). Safety profile has been similar to paclitaxel with myelosuppression as the predominating toxicity. Based on data from patients evaluated to date for intracranial response, 6/30 (20%) patients had a partial response (PR) and 17/30 (57%) had a stable disease (SD). Among patients with leptomeningeal disease, 4/11 (36%) had a PR. The longest duration on treatment is for 18 cycles, seen in a patient with a PR that sustained for 10 cycles. Furthermore, ANG1005 treatment resulted in disease control in extracranial lesions in all 14 evaluated patients (1 PR and 13 SD), even after prior taxane therapy. CONCLUSIONS: The efficacy and safety data to date suggest that ANG1005 is a promising therapy for treatment of brain and leptomeningeal metastases from breast cancer.