Clinical trial data of imetelstat in patients with breast cancer presented at ASCO annual meeting

Geron Corporation (Nasdaq:GERN) today announced the presentation of data from the clinical trial of imetelstat (GRN163L), the company's telomerase inhibitor drug, in combination with paclitaxel and bevacizumab in patients with breast cancer at the 2010 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

“We plan to initiate a randomized Phase 2 breast cancer trial this year to test the effect on progression-free survival of adding imetelstat to this combination regimen. The trial will also explore predictive biomarkers to preferentially select breast cancer patients who may benefit from telomerase inhibition.”

An interim analysis of the Phase 1 trial was presented by Geron clinical scientists and collaborating principal investigators from Ingalls Memorial Hospital, Harvey, IL and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN.

"We are very encouraged by the data from the trial so far. We have seen good tolerability and exposures of drug, which exceed levels that have been associated with tumor inhibition in several models of human cancers. In addition, a preliminary response rate of 54% is promising in context of the reduced doses of chemotherapy that were administered during treatment cycles," said Stephen M. Kelsey, M.D., Geron's executive vice president and chief medical officer, oncology. "We plan to initiate a randomized Phase 2 breast cancer trial this year to test the effect on progression-free survival of adding imetelstat to this combination regimen. The trial will also explore predictive biomarkers to preferentially select breast cancer patients who may benefit from telomerase inhibition."

Phase 1 Trial Design

Data were presented on patients with locally recurrent or metastatic breast cancer that were given imetelstat by two hour intravenous infusions on days one, eight and 15 of 28 day treatment cycles. Dosing started at 160 mg/m² and escalation proceeded to 375 mg/m². The patients also received the chemotherapy combination regimen of 90 mg/m² paclitaxel (Taxol®) on days one, eight and 15, and 10 mg/kg bevacizumab (Avastin™) on days one and 15, both by intravenous infusion. Endpoints of the trial are safety, pharmacokinetics and efficacy. Safety data were presented on 14 patients and preliminary efficacy data were on 13 patients.

Pharmacokinetic and Efficacy Results

The preliminary confirmed overall response rate was 53.8% (95% confidence interval: 28.7% to 77.6%) based on investigator assessment of disease status using the Response Evaluation Criteria in Solid Tumors (RECIST). Median duration of response was 21.7 weeks (7.3 to 48.3 weeks).

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.