ANG1005, a brain penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases.

Document Type

Article

Publication Date

1-22-2020

Publication Title

Clinical cancer research : an official journal of the American Association for Cancer Research

Abstract

PURPOSE: ANG1005, a novel taxane derivative, consists of 3 paclitaxel molecules covalently linked to Angiopep-2, designed to cross the blood-brain and blood-cerebrospinal barriers and to penetrate malignant cells via LRP1 transport system. Preclinical and clinical evidence of efficacy with ANG1005 has been previously shown.

EXPERIMENTAL DESIGN: A multi-center, open-label phase 2 study in adult patients with measurable recurrent brain metastases from breast cancer (BCBM), with or without leptomeningeal carcinomatosis (LC) was conducted (n=72 BCBM; n=28 LC subset). ANG1005 was administered IV at 600 mg/m

RESULTS: Median age was 47.5 years. Safety profile was similar to that of paclitaxel with myelosuppression as the predominating toxicity. Average number of prior CNS directed therapies was 2.6 and 94% of the patients had prior taxane treatment. Patient benefit (stable disease or better) was seen in 77% (intracranial) and 86% (extracranial) of the evaluable patients, with iORR of 15% (investigator) or 8% (independent radiology review). In the LC subset, 79% of the patients had intracranial disease control and estimated median overall survival of 8.0 months (95% CI 5.4 - 9.4).

CONCLUSIONS: Even though the study pre-set rule for iORR per IRF was not met in this heavily pretreated population, a notable CNS and systemic treatment effect was seen in all patients, particularly in LC patients, including symptom improvement and prolonged overall survival compared to historical control.

Clinical Institute

Cancer

Clinical Institute

Women & Children

Department

Oncology

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