Exelixis has reported data from a Phase I trial of XL999 in patients with advanced
solid malignancies. Study results identified a maximum tolerated dose (MTD)
of intravenously administered XL999. When administered every two weeks, this
dose demonstrated preliminary evidence of clinical activity with no cumulative
XL999 has been administered across six dose levels to 23 patients with advanced solid tumors. Both patients treated at the maximum administered dose of 6.4 mg/kg experienced hypertension and Grade 3 to 4 elevations in liver enzyme activity (one with fatal cardiogenic pulmonary edema). At 3.2 mg/kg, side-effects observed included infusion-related hypertension, oral sensitivities, dizziness, and a Grade less than or equal to 2 elevation of liver enzyme activity. In general, toxicities were resolved within 24 hours, except for liver enzyme changes. One patient required prophylactic antihypertensive therapy prior to XL999 dosing.