Geron Corp (GERN) Halts Imetelstat Study in HER2-Negative Breast Cancer; Cits Median PFS in Phase 2
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Geron Corporation (Nasdaq: GERN) today announced that, on the basis of an unplanned interim analysis, it is discontinuing its randomized Phase 2 study of imetelstat in metastatic HER2-negative breast cancer because median progression-free survival (PFS) in the imetelstat arm was shorter than in the comparator arm. The Company also announced that it is continuing its randomized Phase 2 study of imetelstat in advanced non-small cell lung cancer (NSCLC). However, although a separate interim analysis of the NSCLC study suggested a modest trend of efficacy in favor of the imetelstat arm, 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 3 development for NSCLC.
The study in metastatic HER2-negative breast cancer was a randomized, controlled trial of 166 patients in which imetelstat was evaluated in combination with paclitaxel, compared to paclitaxel alone. The primary efficacy endpoint was an estimate of PFS.
In this trial, a scheduled periodic review conducted by Geron's Internal Safety Monitoring Committee reported a greater number of deaths and number of patients discontinuing paclitaxel in the imetelstat arm compared to the control arm. Based on these observations, an unplanned interim analysis of efficacy was performed that showed a median PFS of 6.2 months for patients receiving treatment with imetelstat in combination with paclitaxel, compared to 8.0 months for patients receiving paclitaxel alone (hazard ratio = 1.62; p = 0.028). Although
the absolute number of deaths was higher in the imetelstat arm (16 vs. 10), there was no statistically significant difference in overall survival. Based on these findings, Geron has discontinued this trial.
The clinical trial protocol allowed for reductions or delays in the dosing of paclitaxel consistent with the approved labeling, and there were an increased number of such occurrences in the imetelstat arm of the study. A series of analyses suggested that reductions of paclitaxel dose intensity in the imetelstat arm were likely responsible for the difference in PFS.
To understand the potential effect of imetelstat in the metastatic HER2-negative breast cancer study independent of reduced paclitaxel dosing, and to ensure that treatment with the drug was not accelerating disease progression in the NSCLC trial, Geron conducted an unplanned interim safety and efficacy analysis of the data from its randomized Phase 2 trial in NSCLC where imetelstat is administered as a single agent. The advanced NSCLC study of 116 patients is evaluating imetelstat maintenance treatment following platinum-based induction chemotherapy compared to observation. In this study imetelstat is administered at a higher dose and frequency than in the HER2-negative metastatic breast cancer study.
The interim analysis of the NSCLC study suggested a modest but not statistically significant trend in PFS in favor of the imetelstat arm (hazard ratio = 0.78). The Kaplan-Meier curves separated just before the median, resulting in no meaningful difference in median PFS between the two arms; median PFS for the imetelstat treated arm was 2.8 months, compared to 2.6 months for the observation-only arm. Thus, no evidence was found that imetelstat was accelerating disease progression in this study, which is continuing as planned.
The data from the interim analysis of the NSCLC trial also suggested that imetelstat was not contributing to the increased risk of disease progression independent of reduced paclitaxel dosing in the metastatic breast cancer study. Therefore, at this time, the Company is not aware of any factors responsible for the shorter PFS in the imetelstat treatment arm of the metastatic breast cancer study other than the reduced paclitaxel dose intensity.
Geron's plans for further development of imetelstat in hematologic malignancies have not been adversely impacted by these results. The Company is evaluating imetelstat in two hematologic malignancies: essential thrombocythemia (ET) and multiple myeloma. Using biomarkers, these two studies are designed to evaluate whether inhibiting telomerase will selectively reduce the proliferation of the malignant progenitor cells responsible for these diseases. In the ET trial, the Company is also evaluating clinical and hematological responses. Geron continues to expect to release top-line results from these studies in the fourth quarter of this year.
Geron ended the second quarter of 2012 with $122 million in cash and investments.
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The study in metastatic HER2-negative breast cancer was a randomized, controlled trial of 166 patients in which imetelstat was evaluated in combination with paclitaxel, compared to paclitaxel alone. The primary efficacy endpoint was an estimate of PFS.
In this trial, a scheduled periodic review conducted by Geron's Internal Safety Monitoring Committee reported a greater number of deaths and number of patients discontinuing paclitaxel in the imetelstat arm compared to the control arm. Based on these observations, an unplanned interim analysis of efficacy was performed that showed a median PFS of 6.2 months for patients receiving treatment with imetelstat in combination with paclitaxel, compared to 8.0 months for patients receiving paclitaxel alone (hazard ratio = 1.62; p = 0.028). Although
the absolute number of deaths was higher in the imetelstat arm (16 vs. 10), there was no statistically significant difference in overall survival. Based on these findings, Geron has discontinued this trial.
The clinical trial protocol allowed for reductions or delays in the dosing of paclitaxel consistent with the approved labeling, and there were an increased number of such occurrences in the imetelstat arm of the study. A series of analyses suggested that reductions of paclitaxel dose intensity in the imetelstat arm were likely responsible for the difference in PFS.
To understand the potential effect of imetelstat in the metastatic HER2-negative breast cancer study independent of reduced paclitaxel dosing, and to ensure that treatment with the drug was not accelerating disease progression in the NSCLC trial, Geron conducted an unplanned interim safety and efficacy analysis of the data from its randomized Phase 2 trial in NSCLC where imetelstat is administered as a single agent. The advanced NSCLC study of 116 patients is evaluating imetelstat maintenance treatment following platinum-based induction chemotherapy compared to observation. In this study imetelstat is administered at a higher dose and frequency than in the HER2-negative metastatic breast cancer study.
The interim analysis of the NSCLC study suggested a modest but not statistically significant trend in PFS in favor of the imetelstat arm (hazard ratio = 0.78). The Kaplan-Meier curves separated just before the median, resulting in no meaningful difference in median PFS between the two arms; median PFS for the imetelstat treated arm was 2.8 months, compared to 2.6 months for the observation-only arm. Thus, no evidence was found that imetelstat was accelerating disease progression in this study, which is continuing as planned.
The data from the interim analysis of the NSCLC trial also suggested that imetelstat was not contributing to the increased risk of disease progression independent of reduced paclitaxel dosing in the metastatic breast cancer study. Therefore, at this time, the Company is not aware of any factors responsible for the shorter PFS in the imetelstat treatment arm of the metastatic breast cancer study other than the reduced paclitaxel dose intensity.
Geron's plans for further development of imetelstat in hematologic malignancies have not been adversely impacted by these results. The Company is evaluating imetelstat in two hematologic malignancies: essential thrombocythemia (ET) and multiple myeloma. Using biomarkers, these two studies are designed to evaluate whether inhibiting telomerase will selectively reduce the proliferation of the malignant progenitor cells responsible for these diseases. In the ET trial, the Company is also evaluating clinical and hematological responses. Geron continues to expect to release top-line results from these studies in the fourth quarter of this year.
Geron ended the second quarter of 2012 with $122 million in cash and investments.
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