Geron reported a pair of disappointing Phase II trial results this morning concerning its experimental telomerase inhibitor imetelstat (GRN163L), saying it would halt one trial and not advance a second into Phase III as previously planned.
The results come less than a year after Geron CEO John Scarlett repositioned the company as a cancer drug developer focused on imetelstat as well as GRN1005, a peptide-drug conjugate designed to fight brain cancer. Citing financial pressures, Geron sidelined its stem cell development programs and axed 38% of its workforce [GEN News Highlights, Nov. 15, 2011: http://www.genengnews.com/gen-news-highlights/b-geron-b-sidelines-stem-cell-programs-and-cuts-workforce-to-focus-on-b-b/81245957/].
Halted today was Geron’s Phase II study of imetelstat in metastatic HER2-negative breast cancer—a randomized, controlled trial of 166 patients in which imetelstat was evaluated in combination with paclitaxel, and compared to treatment with paclitaxel alone.
After a scheduled periodic review by Geron's Internal Safety Monitoring Committee found more deaths and more patients discontinuing paclitaxel in the imetelstat arm compared to the control arm, the company conducted an unplanned interim efficacy analysis. It showed a median PFS of 6.2 months for patients treated with imetelstat combined with paclitaxel, compared to 8.0 months for patients receiving paclitaxel alone. Number of deaths was higher in the imetelstat arm (16 vs. 10), with no corresponding statistically significant difference in overall survival.
Geron said reductions of paclitaxel dose intensity in the imetelstat arm were likely responsible for the difference in PFS.
The company also conducted an unplanned interim safety and efficacy analysis of data from its randomized Phase 2 trial in non-small cell lung cancer (NSCLC) where imetelstat is administered as a single agent, since the telomerase inhibitor is being administered at a higher dose and frequency than in the breast cancer study.
The advanced NSCLC study of 116 patients is evaluating imetelstat maintenance treatment following platinum-based induction chemotherapy compared to observation. Interim analysis suggested a modest but not statistically significant trend in PFS in favor of the imetelstat arm (2.8 months) compared with the observation-only arm (2.6 month), with no meaningful difference in median PFS between the two arms.
“The pre-specified success criteria in this trial are unlikely to be met, and, as a consequence, it is doubtful that Geron will take imetelstat forward into Phase [III] development for NSCLC,” Geron said in a statement.
The company added that its NSCLC study would continue Phase II since no evidence was found that imetelstat was accelerating disease progression.