Abstract 4526: IG-001 - Evaluation as next generation nanoparticle paclitaxel against poorly perfused tumors.
Authors: Trieu Vuong , Hwang Larn , Motamed Kouros , Hsiao Chao 
Published: August 2014

Study Purpose: nab-paclitaxel (Abraxane), though a breakthrough in paclitaxel formulation, has inherent problems associated with any biologics. IG-001, being a chemical polymer bound nanoparticle paclitaxel instead of biological polymer, is being developed as the next generation nanoparticle paclitaxel. Its target indications are difficult to perfuse hypoxic tumors such as pancreatic cancer, taking advantage of its ability to rapidly deliver paclitaxel to the targeted tissue via albumin mediated transport. This presentation details the identification of characteristics necessary for activity of nanoparticle paclitaxel and comparison between IG-001 and nab-paclitaxel.

Methods: Preclinical and clinical PK of the various formulations were compared to define the defining characteristics of an effective nanoparticle paclitaxel ie. nab-paclitaxel. The pharmacokinetic parameters were estimated by using the noncompartmental open model and the WinNonlin program (Pharsight Corp., Mountain View, CA). Descriptive statistics were computed for PK assessment. Regression analysis of AUCinf vs. dose was performed to gain an appreciation of dose proportionality. Tumor xenografts studies against Melanoma (B16F10), Breast (MDAMB435S, MX-1), Ovarian (SKOV3), and Pancreatic (MIA PaCa-2, PANC-1) were also examined. Tumor inhibition relative to Taxol was used to normalize across tumor types.

Results: The defining characteristics of nab-paclitaxel are its rapid tissue penetration such that tumor/plasma drug ratio was greater than Taxol with 1.9 fold advantage for nab-paclitaxel. Formulations with tumor accumulation greater than Taxol without corresponding high tumor/plasma ratio were ineffective. IG-001 and nab-paclitaxel exhibited the similar profiles: high tissue penetration, high tumor/plasma ratio, dose proportional PK in human, higher MTD in tumor xenograft studies, higher MTD during phase I dose escalation study in human. Correspondingly IG-001 and nab-paclitaxel have similar activities in tumor xenografts models- higher MTD and better efficacy at equitoxic dose versus Taxol. More importantly, IG-001 exhibited activity against poorly perfused pancreatic xenografts (MIAPaCa-2, PANC-1).

Conclusions: A non-albumin-based paclitaxel formulation (IG-001) was found to have similar properties to the albumin-based paclitaxel formulation (nab-paclitaxel). Its clinical development could give us the next generation paclitaxel nanoparticle formulation that can be more readily modified than nab-paclitaxel (Abraxane). More importantly, this model could be used to develop other nanoparticle drugs against difficult to perfused tumors such as pancreatic cancers.

Citation Format: Vuong Trieu, Larn Hwang, Kouros Motamed, Chao Hsiao. IG-001 - Evaluation as next generation nanoparticle paclitaxel against poorly perfused tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4526. doi:10.1158/1538-7445.AM2013-4526