Introduction: nab-paclitaxel–a Cremophor-free, albumin-bound, nanoparticle form of paclitaxel–though a breakthrough in paclitaxel formulation, has inherent problems associated with any biologics. IG-001 (Cynviloq/Genexol-PM), a polymeric albumin-free micellar formulation utilizes biodegradable di-block copolymers composed of methoxy poly (ethylene glycol)-poly (lactide) to form nanoparticles with paclitaxel and is being developed as the next generation nanoparticle paclitaxel. Its target indications are solid tumors such as Breast, NSCLC, Ovarian, Bladder and Pancreatic cancers, taking advantage of its ability to rapidly deliver paclitaxel to the targeted tissue via albumin-mediated transport, as previously described for nab-paclitaxel. Herein, we report preclinical and dissolution stability of IG-001 in comparison to nab-paclitaxel in the ovarian cancer setting.

Methods: Preclinical PK parameters (HL, Tmax, AUCinf, Vz and CL) of the two formulations were compared following bolus IV and IP injections (30 mg/kg) in mice. Blood paclitaxel concentration was quantified using LC/MS/MS method and PK parameters were obtained using the Phoenix PK program (Pharsight, CA). Dissolution studies of nab-paclitaxel and IG-001 were performed using the drug products reconstituted in saline and diluted in PBS or plasma. Particle stability was monitored by dynamic light scattering using the Malvern Nanosizer.

Results: IG-001 exhibited conditional stability, wherein stability was high in PBS and Lactated Ringer's solution but very low in plasma. In contrast, nab-paclitaxel exhibited the expected instability in both plasma and PBS. Across multiple experiments, there was about a 10-fold enhancement of particle stability in serum-free matrices. This suggests that IG-001 may have a PK advantage over nab-paclitaxel when administered as saline-reconstituted solution into the peritoneal cavity for the treatment of ovarian cancer. Therefore, a PK study was performed in mice with drugs administered IP and IV. The bolus IV injection studies in mice revealed almost identical PK parameters for the two formulations. However, IP injection studies indicated about a 10-fold enhanced paclitaxel levels for IG-001 vs. nab-paclitaxel up to 1 hour post administration. Thereafter, it was not possible to determine IP paclitaxel levels due to complete absorption of the administered drug solution.

Conclusions: Collectively, our data strongly supports the notion that the conditional stability of IG-001 would confer an advantage in ovarian indication wherein the drug is administered IP as a saline reconstituted drug solution. It also suggests that the observed preferential peritoneal accumulation of paclitaxel when Taxol was administered may not be applicable to nab-paclitaxel due to the absence of Cremophor-EL as a sequestering agent in the peritoneal cavity.

Citation Format: Kouros Motamed, Rosemary Kim, Hyunjoung Yang, Vuong Trieu. IG-001 potential as intraperitoneal therapy for ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5414. doi:10.1158/1538-7445.AM2014-5414