Exelixis reports encouraging data from Phase I leukemia trial

Approximately 17 subjects have received at least one dose of XL228, of whom 16 had completed cycle 1. The trial is evaluating a treatment cycle consisting of four weekly one-hour IV infusions of XL228 at doses ranging from 0.45mg/kg to 7.2mg/kg. Approximately 13 of the 17 subjects (76.5%) have BCR-ABL mutations, including seven (41.2%) with the T315I mutation.

At the 3.6 and 7.2mg/kg doses, all subjects have demonstrated stable or decreasing white blood cell counts. A chronic myelogenous leukemia (CML) patient with an F317L BCR-ABL mutation in lymphoid blast crisis experienced a marked decrease in peripheral blast counts on XL228 (7.2mg/kg) and hydroxyurea which was maintained despite decreasing use of hydroxyurea. Two patients have demonstrated prolonged stable disease for more than eight months.

XL228 is a small molecule inhibitor of BCR-ABL, SRC, and insulin-like growth factor type 1 receptor (IGF1R), which is associated with cancer cell proliferation, survival, and metastasis. The compound also potently inhibits the T315I mutant form of BCR-ABL, which is resistant to all currently approved inhibitors.

Michael Morrissey, president of R&D at Exelixis, said: “These data suggest that XL228 may have important clinical utility for patients with CML or Philadelphia chromosome-positive acute lymphocytic leukemia, including those resistant or intolerant to current therapeutics.”