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.