Phase 2/3 Clinical Trial to Evaluate Imetelstat in Transfusion-Dependent Participants With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) That is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
This clinical trial was originally conducted by Janssen Research and Development (Janssen) under a collaboration agreement (see Partners). Geron will assume responsibility for this clinical trial once the investigational new drug (IND) sponsorship has transferred back to Geron.
IMerge is a two-part clinical trial of imetelstat in transfusion dependent patients with Low or Intermediate-1 risk, also referred to as lower risk, MDS, who have relapsed after or are refractory to prior treatment with an ESA. Part 1 of IMerge was designed as a Phase 2, open label, single arm study to assess the efficacy and safety of imetelstat. Imetelstat was administered as an intravenous infusion at a starting dose of 7.5 mg/kg every four weeks in approximately 30 patients. The primary endpoint is the rate of red blood cell (RBC) transfusion independence (TI) for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.
Part 2, or the Phase 3 portion of IMerge, is designed as a randomized, double-blind, placebo-controlled clinical trial with approximately 170 patients that will be randomized in a 2:1 ratio to receive either imetelstat or placebo. Dosing as well as primary and secondary endpoints are the same for both Part 1 and Part 2 of IMerge.
The first patient in the Phase 2 portion of IMerge was dosed in January 2016. 32 patients were initially enrolled in the Phase 2 portion of IMerge, of which 13 patients had not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide and did not have a deletion 5q chromosomal abnormality (non-del(5q)). Preliminary data from the Phase 2 portion of IMerge were presented at the European Hematology Association Annual Congress in June 2018. The data showed that the 13-patient initial cohort exhibited an increased rate and durability of transfusion independence compared to the overall trial population (8-week RBC-TI rate: 54% vs. 34%).
To increase the clinical experience and confirm the benefit-risk profile of imetelstat in the initial 13-patient cohort, enrollment was expanded to include 25 additional patients in an expansion cohort who were non-del(5q) and naive to HMA and lenalidomide treatment. In November 2017, the first patient was dosed in the expanded Phase 2 portion of IMerge and enrollment was completed in February 2018.
Detailed results from the combined initial cohort of 13 patients and the expansion cohort of 25 patients (n=38) were presented at the American Society of Hematology Annual Meeting in December 2018.
The Phase 2 portion of IMerge has been officially closed to new patient enrollment and patients remaining in the treatment phase are eligible to continue to receive imetelstat treatment, per investigator discretion. Data collection and patient follow-up continue in accordance with the trial protocol. More mature data is expected to be presented at a medical conference in 2019.
Based on results of the Phase 2 portion of IMerge, Geron plans to open for enrollment the Phase 3 portion of IMerge by mid-year 2019.
To learn more about this study, including enrollment criteria, locations and current status, visit ClinicalTrials.gov.
Imetelstat, a telomerase inhibitor, is an investigational treatment for cancer and has not been approved by the FDA or any other regulatory agency.
IMerge Study Design