Exilixis' phase 1 trial of XL999 sets dosing levels, shows evidence of action against tumors

New York, Nov. 17 - Exilixis, Inc. reported a phase 1 trial of its XL999 treatment in patients with advanced solid malignancies identified a maximum tolerated dose, showed evidence of action against tumors and resulted in no build up of toxic products.

"We are very excited by these results and look forward to evaluating XL999 further in a broad targeted phase 2 clinical program, which we intend to initiate very soon," said George A. Scangos, president and chief executive officer of Exelixis, in a news release.

"Preliminary clinical activity has been observed even in this population of heavily pre-treated patients. Based on safety and PK [pharmacokinetic] data and the clinical signals we have seen in our study, a weekly dosing schedule is being explored, and phase 2 trials to evaluate the potential of XL999 are warranted," added Dr. Kyriakos Papadopoulos, clinical investigator at the Institute for Drug Development Cancer Therapy and Research Center.

Papadopoulos presented the trial results in a poster presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

In the study, XL999 was administered intravenously at six dose levels (0.2, 0.4, 0.8, 1.6, 3.2 and 6.4 mg/kg) to 23 patients with advanced solid tumors.

Both patients treated at the maximum 6.4 mg/kg experienced hypertension and grade 3-4 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 grade less than or equal to two elevation of liver enzyme activity. In general, toxicities resolved within 24 hours except for liver enzyme changes. One patient required prophylactic antihypertensive therapy prior to XL999 dosing.

The 3.2 mg/kg dose was determined to be the maximum tolerated dose.

In 22 evaluable patients who have so far been followed for eight weeks or more, there have been two partial responses (liver, thyroid), one minor response (28% reduction, renal cell), and four patients with stable disease for three to seven months (two with thyroid, two with renal cell).

XL999 is a Spectrum Selective Kinase Inhibitor, a potent inhibitor of key receptor tyrosine kinases implicated in the development and maintenance of tumor vasculature and in the proliferation of some tumor cells. In several preclinical models of human tumors, including breast, lung, colon and prostate cancer, XL999 demonstrated potent inhibition of tumor growth, and also caused regression of large well-established tumors.

Exilixis is a Philadelphia-based biotechnology company.

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