Infinity Pharmaceuticals initiates Phase II breast cancer trial

Infinity Pharmaceuticals has initiated a Phase II clinical trial of IPI-504, its lead heat shock protein 90 inhibitor, in combination with Herceptin in patients with human epidermal growth factor receptor 2-positive breast cancer.

IPI-504 has demonstrated the potential to disrupt the activity of multiple proteins and cell signaling pathways implicated in tumor growth, including human epidermal growth factor receptor 2 (HER2), a key signaling pathway in breast cancer, the company said.

The goal of this open-label, international, multi-center Phase II clinical trial is to evaluate the safety and antitumor activity of IPI-504 in combination with Herceptin in patients with pretreated, locally advanced or metastatic HER2-positive breast cancer. IPI-504 is being administered intravenously at 300mg/m2 on a three-week cycle, consisting of twice-weekly treatment for two weeks followed by one week off treatment.

Herceptin will be administered intravenously once every three weeks. Evidence of antitumor activity will be evaluated using response evaluation criteria in solid tumors. The Phase II study will enroll a total of 46 patients and Infinity anticipates presenting preliminary data in mid-2010.

Infinity said that it is evaluating the potential of heat shock protein 90 (Hsp90) inhibition in a broad range of cancers. The Ring trial is an international Phase III registration trial in patients with refractory gastrointestinal stromal tumors that positions IPI-504 as the potential first-in-class Hsp90 inhibitor. IPI-504 is also being evaluated in a Phase II study in patients with advanced non-small cell lung cancer and in a Phase Ib combination study with Taxotere in patients with advanced solid tumors.

Infinity anticipates presenting data from both of these studies in mid-2009. Infinity is also evaluating its oral hsp90 inhibitor, IPI-493, in a Phase I study in patients with advanced solid tumors, and anticipates reporting preliminary data from this study by the end of 2009.

David Grayzel, vice president of clinical development and medical affairs at Infinity, said: We believe the demonstrated potency and tumor growth inhibition we’ve seen in preclinical models of HER2-positive breast cancer with IPI-504 and the sensitivity of the HER2 protein to Hsp90 inhibition could position anti-chaperone therapy as a key component in the treatment of HER2-positive breast cancer.