ANG1005 is a new generation taxane created from Angiochem's Engineered Peptide Compound (EPiC) platform. Studies have shown that ANG1005 gains entry into the brain compartment by targeting the low‐density lipoprotein receptor‐related protein (LRP) which is one of the most highly expressed receptors on the surface of the BBB. Once inside the brain, ANG1005 enters tumor cells using the same receptor‐mediated pathway through LRP, which is upregulated in various cancer cells including metastatic brain cancer cells. Metastatic brain cancer is the most common intracranial neoplasm in adults with an estimated incidence of 200 000 cases each year in the United States alone. To date, treatment options are limited and marginally effective. A multi‐center, phase I, open‐label, sequential cohort, dose escalation study of ANG1005 in patients with advanced solid tumors and brain metastases is ongoing in the US. Study objectives include characterization of safety and tolerability and identification of maximum tolerated dose (MTD). ANG1005 is administered by IV infusion once every 21 days (1 treatment cycle) without premedication. After evaluating doses of 30–700 mg/m2, 650 mg/m2 was identified as MTD. Data including adverse events and hematological parameters indicate that ANG1005 is safe and well tolerated. The most common events occurring at a severity ≥ Grade 2 according to CTCAE, version 3.0 at MTD (n=20) were neutropenia (95% of patients; Grade 4 in 75%), leucopenia (100%; Grade 4 in 40%), anemia (55%; no cases of Grade 4), thrombocytopenia (40%; no cases of Grade 4) and mucositis (25%; no cases of Grade 4); these events have been transient and manageable with standard treatments. Neurocognitive data have shown that ANG1005 does not cause cognitive impairment and tests for antibodies demonstrate that ANG1005 does not elicit antibody production even in patients who have received up to 6 cycles of treatment. Pharmacokinetic data indicate linear ANG1005 bioavailability. Disease control (≥ stable disease) assessed by CT/MRI in this heavily pre‐treated group of patients was achieved in 70% at doses > 300 mg/m2 including 7 patients who had previously progressed on taxane therapy. Partial response was observed in 30% of patients dosed > 300 mg/m2. Tumor types that showed the best improvements were breast, non‐small cell lung and ovarian cancers. Furthermore, partial and complete responses were achieved in metastatic locations including the brain (67% disease control), liver (70% disease control), lung (67% disease control) and lymph nodes (80% disease control). Clinical data gathered to date indicate that ANG1005 shows promise as a potential treatment option for patients with advanced solid tumors and brain metastases.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B168.
- Copyright © 2009, American Association for Cancer Research