The heat shock chaperone protein (HSP-90) has emerged as a promising target for cancer therapy. Infinity Pharmaceuticals’ IPI-504 is one of many experimental heat shock protein inhibitors vying for a spot in the cancer market. Data from the recently completed Phase I trial of this drug was presented at the 2008 American Society of Clinical Oncology conference (ASCO) in May. Based on this information, Infinity Pharmaceuticals has announced plans to initiate an international Phase III registration trial of its HSP-90 inhibitor, IPI-504, in patients with refractory GIST in the third quarter.

The Phase III protocol has been granted a Special Protocol Assessment agreement by the Food and Drug Administration (FDA). The European Medicines Evaluation Agency has provided scientific advice consistent with that of the FDA regarding the Phase III trial design. To participate in this trial, patients must have failed both imatinib and sunitinib therapy. There will be no limit to the number of prior therapies patients may have received. The company has also assured us that patients will be screened according to the inclusion/ exclusion criteria to make certain that patients with large tumor loads will be excluded and not subject to undue risk.

The trial will be randomized and will use a placebo control with a crossover upon progression. The trial design calls for a 2:1 ratio, with the 66 percent of patients, or 130 of the 195 accrued patients, assigned to the IPI-504 treatment arm. Thirty-three percent will be on the placebo arm. The placebo patients will have a one week washout period before trial start.

On the trial, patients will receive 400 mg/m2 of IPI-504 (or placebo) as a 30- minute intravenous infusion twice weekly for two weeks followed by one week off with best supportive care. The first status evaluation will include a CT scan approximately two weeks into the trial.

The IPI-504 trial design includes plans to use centralized CT scan review to insure both consistency and accuracy in measuring potential progression and timely turn-around. Plans include scans at two, five, and eight weeks with a one week turn-around. Four to six radiologists will read the scans and compare results. Results will be transmitted electronically for review by the primary site (Dana-Farber Cancer Institute). Infinity has provided assurance of best effort in monitoring all patients for progression so that crossover can be timely for those patients on placebo.

This article is based on a May 30, 2008 meeting with Norman Scherzer, Jim Hughes and representatives from Infinity Pharmaceuticals and subsequent telephone discussions with Infinity.