Cabazitaxel is an approved treatment for castration-refractory prostate cancer. As with other taxanes, the therapeutic benefits of cabazitaxel are often compromised by immunosuppression and neurotoxicity. In order to address the obstacles to using cabazitaxel, we developed the dynamic tumor-targeted cabazitaxel nanopharmaceutical CRLX522. This nanopharmaceutical possesses significantly enhanced efficacy and improved pharmacokinetics compared to the parent drug. CRLX522 showed a superior PK profile, with a >400-fold increase in AUC, a significantly longer half-life and a 32-fold higher drug concentration in tumor tissue 72 hours after a single administration versus cabazitaxel alone. The improved PK and biodistribution of CRLX522 translated into superior antitumor activity in murine syngeneic and human xenograft models. In the murine B16.F10 tumor model, median survival at the MTD exceeded 58 days for CRLX522 compared to 26 days for the parent drug cabazitaxel. CRLX522 demonstrated superior efficacy over cabazitaxel with a cure rate of 100% in a xenograft model representing breast cancer tumors, compared to 50% cures for the parent drug cabazitaxel. In summary, CRLX522 represents a new and potent anticancer therapeutic that has the potential to be a best-in-class taxane.

Citation Format: Douglas Lazarus, Sujan Kabir, Scott Eliasof. CRLX522, a novel dynamic tumor-targeted cabazitaxel nanopharmaceutical. [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 4582. doi:10.1158/1538-7445.AM2014-4582