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

 

trial Design

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 IMerge Phase 3 clinical trial, 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.

Current Status

The first patient in the IMerge Phase 2 clinical trial was dosed in January 2016. 32 patients were initially enrolled in the Phase 2, 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 IMerge Phase 2 clinical trial 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 European Hematology Association Annual Congress in June 2019.  

The IMerge Phase 2 clinical trial 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.

Geron opened enrollment for the IMerge Phase 3 clinical trial in August 2019. The first patient was dosed in October 2019.

To learn more about this trial, 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.