ANG1005, a brain penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases.
Clinical cancer research : an official journal of the American Association for Cancer Research
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.
Women & Children
Kumthekar, Priya; Tang, Shou-Ching; Brenner, Andrew J; Kesari, Santosh; Piccioni, David E; Anders, Carey K; Carrillo, Jose A; Chalasani, Pavani; Kabos, Peter; Puhalla, Shannon L; Tkaczuk, Katherine H R; Garcia, Agustin; Ahluwalia, Manmeet S; Wefel, Jeffrey S; Lakhani, Nehal; and Ibrahim, Nuhad K, "ANG1005, a brain penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases." (2020). Articles, Abstracts, and Reports. 2712.