Pharmacokinetic (PK) profile of imetelstat in combination therapy with paclitaxel and bevacizumab was comparable to the PK profile of imetelstat administered alone (from the Phase 1 trial in solid tumors). In the solid tumor trial, the observed level of exposure to imetelstat during the treatment period (AUC) was higher than the exposure that was associated with inhibition of telomerase activity and tumor growth in multiple xenograft animal models of human cancers. Similarly, in this Phase 1 combination trial in breast cancer, modeled AUC values at doses of imetelstat from 240 mg/m2 and above also exceeded the exposure required for efficacy in preclinical models.

Safety Results

Infusions of imetelstat were generally well tolerated and acute dose limiting toxicities were not observed. Neutropenia (low neutrophils) and/or thrombocytopenia (low platelets) in later treatment cycles led to reductions in the dose of imetelstat and/or paclitaxel in 12 (85.7%) patients. Alternative dosing schedules are being evaluated in additional patients to further increase exposure to imetelstat and to enable administration of full doses of standard therapy while minimizing hematological toxicities.

Phase 2 Trial

A randomized Phase 2 clinical trial of imetelstat in patients with metastatic breast cancer is planned for the fourth quarter of 2010. The trial plans to assess the effect on progression-free survival of adding imetelstat to paclitaxel and bevacizumab as first line therapy. The trial will recruit approximately 150 patients from up to 50 medical centers in the U.S.

SOURCE Geron Corporation