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/m2 q3w. Tumor assessment was based on CNS RECIST 1.1 for intracranial, and RECIST 1.1 for extracranial response. The primary endpoint was determination of intracranial objective response rate (iORR).
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.
Copyright ©2020, American Association for Cancer Research.
ANG1005 for Breast Cancer Brain Metastases: Correlation Between 18 F-FLT-PET After First Cycle and MRI in Response AssessmentCC O'Sullivan et al. Breast Cancer Res Treat 160 (1), 51-59. PMID 27620882. - Clinical TrialANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and 18F-FLT-PET imaging.
Uptake of ANG1005, a Novel Paclitaxel Derivative, Through the Blood-Brain Barrier Into Brain and Experimental Brain Metastases of Breast CancerFC Thomas et al. Pharm Res 26 (11), 2486-94. PMID 19774344.The results demonstrate that ANG1005 shows significantly improved delivery to brain and brain metastases of breast cancer compared to free paclitaxel.
Antitumour Activity of ANG1005, a Conjugate Between Paclitaxel and the New Brain Delivery Vector Angiopep-2A Régina et al. Br J Pharmacol 155 (2), 185-97. PMID 18574456.These results demonstrate the antitumour potential of a new drug, ANG1005, and establish that conjugation of anticancer agents with the Angiopep-2 peptide vector could in …
Current Challenges in the Management of Breast Cancer Brain MetastasesCC O'Sullivan et al. Semin Oncol 44 (2), 85-100. PMID 28923217. - ReviewApproximately 50% of patients with advanced human epidermal growth factor 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC) ultimately develop brea …
Efaproxiral: GSJ 61, JP 4, KDD 86, RS 4, RSR 13Drugs R D 6 (3), 178-85. PMID 15869322. - ReviewEfaproxiral [RSR 13, GSJ 61, JP 4, KDD 86, RS 4] is a synthetic, small-molecule, radiation-sensitising agent being developed by Allos Therapeutics primarily for the treat …