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  Phase 2/3 clinical trial evaluating 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, or IMerge Phase 2, was designed as an open label, single arm trial 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. 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 IMerge Phase 3, is designed as a randomized, double-blind, placebo-controlled clinical trial in approximately 170 patients with lower risk transfusion dependent MDS who are relapsed or refractory to an ESA, have not received prior treatment with either an HMA or lenalidomide and are non-del(5q) 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 IMerge Phase 2 and IMerge Phase 3. Based on discussions with U.S. and European regulatory authorities, if the results from IMerge Phase 3 are successful, we expect such data to support the registration of imetelstat in lower risk MDS.

CURRENT STATUS OF IMERGE PHASE 3

IMerge Phase 3 opened for patient screening and enrollment in August 2019, and the first patient was dosed in October 2019. As of August 12, 2021, we attained 91% of the planned patient enrollment. IMerge Phase 3 is open for patient screening and enrollment and is being conducted at over 100 medical centers globally, including North America, Europe, Middle East and Asia.

To learn more about this trial, including enrollment criteria, locations and current status, visit ClinicalTrials.gov.

CURRENT STATUS OF IMERGE PHASE 2

IMerge Phase 2 is 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.

Thirty-two 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.

More mature data  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 2020, American Society of Hematology Annual Meeting in December 2020 and were published in the Journal of Clinical Oncology in October 2020.

Imetelstat, a telomerase inhibitor, is an investigational treatment for cancer and has not been approved by the FDA or any other regulatory agency.