IG-001—A Non-Biologic Micellar Paclitaxel Formulation for the Treatment of Metastatic Breast Cancer

Abstract

Introduction: IG-001 (Genexol-PM), utilizes biodegradable di-block copolymers composed of methoxy poly (ethylene glycol)-poly (lactide) to form micellar nanoparticles with paclitaxel containing a hydrophobic core and a hydrophilic shell and is being developed as the next generation nanoparticle paclitaxel. Its target indications are solid tumors such as Metastatic Breast Cancer (MBC), Lung, Ovarian, Bladder, Pancreatic and Melanoma. Herein, we have provided the results of clinical experience with IG-001 in MBC available to date through summaries of two completed Phase 2 studies, an ongoing Phase 3 study and a completed post-marketing surveillance (PMS) study. Results: Results of the two completed safety and efficacy single-arm Phase 2 studies revealed ORRs of 28.1% and 58.5% in anthracyclin-resistant MBC patients and those with histologically-confirmed MBC, respectively. The interim analysis of an ongoing dual-arm Phase 3 data (106 patients/arm) receiving either Taxol (175 mg/m2) or IG-001 (300mg/ m2) over a 3 hour period every 3 weeks for 6 cycles has revealed a superior ORR of IG-001 (40%) vs. Taxol (26%). This superiority over Taxol was very comparable to the historical data from Abraxane® trials. Lastly, results of the PMS study of IG-001 in 186 enrolled paients with locally recurrent or MBC showed an overall efficacy rate of 24.32% (36/148 evaluable subjects with partial responses). Twenty one subjects (11.29%) reported a total of 34 serious adverse events. The most frequent were neutropenia (1.61%), febrile neutropenia (1.61%), headache (1.61%), vomiting (1.08%), fever (1.08%), dyspnea (1.08%) and tachycardia (1.08%).Most of these were secondary to expected toxicities of the study drug. Peripheral neuropathy was common but was not dose-limiting in most cases. Hematological toxicities were manageable (3 subjects with febrile neutropenia). Conclusions: Taken together, in patients with metastatic breast cancer who have been previously treated with chemotherapy, including anthracycline containing regimens, the efficacy of IG-001 appears to be similar and at least equal to that of Abraxane®. Further development of IG-001 is therefore warranted in Breast cancer as well as other solid tumors.