CT-2103: A Novel Macromolecular Taxane with Potential Advantages Compared with Conventional Taxanes

Abstract

CT-2103 (Xyotax™) is a polymer–drug conjugate designed to improve upon the therapeutic index and tolerability of conventional taxanes. Because standard chemotherapy drugs distribute randomly in the body, both tumor and normal tissues are exposed to the cytotoxic effects of these drugs. In contrast, conjugation of low molecular weight drugs, such as paclitaxel, to a polymer results in significant passive tumor targeting by the enhanced permeability and retention effect. Moreover, appropriately designed polymer–drug conjugates form polymeric prodrugs that are inert during transport. The release of the active drug is dependent on cleavage of the polymer backbone following endocytic uptake of the conjugate into tumor cells. Preclinical studies show that CT-2103 accumulates in the tumor tissue and that paclitaxel is slowly and progressively released from the polymer. Clinical pharmacokinetics data show that CT-2103 is stable in plasma; data are consistent with prolonged tumor exposure and reduced systemic exposure to active drug. Based on the promising results in phase I/II studies, 3 phase III trials of CT-2103 were initiated in advanced non–small-cell lung cancer (NSCLC). These Selective Targeting for Efficacy in Lung Cancer, Lower Adverse Reaction (STELLAR™) trials represent the largest randomized phase III programs in patients with NSCLC and a poor performance status.