Phase 2 Clinical Trial of Imetelstat in Essential Thrombocythemia, Geron (GERN)

GERN enrolled the 1st patient in a P2 clinical trial to evaluate the activity of its telomerase inhibitor drug, imetelstat (GRN163L) in patients with essential thrombocythemia (ET).

The Phase 2 clinical trials of imetelstat are focused on malignancies in which cancer stem cells are thought to play an important role in disease progression, including breast and lung cancers, multiple myeloma and myeloproliferative neoplasms, such as essential thrombocythemia. 

The clinical trial is a Phase 2, open-label study of imetelstat as a single agent in patients with ET who have failed or are intolerant to at least 1 prior therapy or who refuse standard therapy, such as hydroxyurea, anagrelide or interferon-alpha.

• The primary efficacy endpoint is best overall hematologic response rate, determined by a normalization or reduction in platelet counts;
•  Approximately half of patients with ET have a molecular mutation in the JAK2 or MPL genes;
• The rate of molecular response is a secondary endpoint in patients who have one or both of these mutations at baseline;
• A molecular response is determined by a reduction in the percentage of mutant JAK2 or MPL alleles detected in patients’ granulocytes;
• Safety and tolerability will also be assessed;
• Patients in the trial will be stratified based on the presence or absence of mutations in the JAK2 and MPL genes;
• Imetelstat is administered at an initial dose of 7.5 mg/kg weekly in a 28 day treatment cycle. The dose may be escalated to 9.4 mg/kg and up to a maximum of 11.7 mg/kg weekly, depending on hematologic response and tolerability. Dose and dosing schedule will be titrated based on platelet counts;
• The trial will be conducted at clinical sites in the US and EU. The lead principal investigator is Srdan Verstovsek, M.D., Ph.D., at The University of Texas, MD Anderson Cancer Center in Houston, Texas.

ET is a chronic disorder that arises in the hematopoietic (blood) stem cells in the bone marrow. The leukemic stem cells produce aberrant clones of platelet-forming cells (megakaryocytes), which results in increased numbers of circulating platelets.