Imetelstat: Phase II data

Geron discontinued an open-label Phase II trial in 166 patients with locally recurrent or metastatic HER2-negative breast cancer after an unplanned interim analysis showed that median PFS, the primary endpoint, was significantly shorter in patients receiving imetelstat plus paclitaxel vs. paclitaxel alone (6.2 vs. 8 months, p=0.028). At the time of the interim analysis, 85 progression events had occurred, or 91% of the pre-specified 93 events required for the primary endpoint analysis. Geron's internal safety monitoring committee conducted the interim analysis after it reported a greater number of deaths and patients discontinuing paclitaxel in the imetelstat arm vs. the control arm. There were 16 deaths in the imetelstat plus paclitaxel arm and 10 deaths in the paclitaxel alone arm, although there was no significant difference in OS between treatment groups. The objective response rate (ORR) was 48% in patients receiving imetelstat plus paclitaxel vs. 41% in patients receiving paclitaxel alone. There were 2 complete responses in each treatment arm.

Geron said that a series of analyses suggested that reductions of paclitaxel dose intensity in the imetelstat arm were likely responsible for the difference in PFS. The company estimated that patients in the imetelstat arm received about 85% of the amount of paclitaxel that patients in the control arm received. Geron said it believes that the reduced paclitaxel dosing was predominantly the result of hematologic toxicity induced by imetelstat in combination with paclitaxel. Patients received 300 mg/m 2 imetelstat on day 1 of a 21-day cycle plus paclitaxel with or without Avastin bevacizumab or paclitaxel alone with or without Avastin. ...