The REMARK trial aims to assess the safety and efficacy of RVU120 in patients with lower-risk myelodysplastic syndromes.
Trial Name: A Phase II, Open-label, Multicenter Study of Orally Administered RVU120 for the Treatment of Anemia in Patients With Lower-risk Myelodysplastic Neoplasms (MDS)
ClinicalTrials.gov Identifier: NCT06243458
Sponsor: GCP-Service International West GmbH
Recruitment Contact: Andreas Beust, +49 (0) 421 89 67 66 11, germany@gcp-service.com
Completion Date: May 2027
The first patient with lower-risk myelodysplastic syndromes (LR-MDS) has been dosed with RVU120 in the phase 2 REMARK study (NCT06243458).1
"I am proud that we could start the REMARK study in line with our ambitious plans. RVU120 has shown promising hematologic improvement in patients with off-hematologic impaired bone marrow function. I am optimistic that this clinical evidence will translate into a positive outcome of the REMARK study. RVU120 has important features that should be considered a potential new treatment option for patients with LR-MDS. It may aid in achieving our ultimate aim to alleviate the need for red blood cell transfusions in these patients,” said Uwe Platzbecker, MD, director of the Clinic and Poliklinik for Hematology, Cell Therapy and Hemostaseology at the Leipzig University Hospital, in a press release.
REMARK is a phase 2, open-label, multicenter, investigator-initiated study being done through the European Myelodysplastic Neoplasms Cooperative Group (EMSCO) network. Up to 25 clinical sites will be included in the study globally, and the planned overall enrollment is up to about 40 patients.
RVU120, a novel small-molecule CDK8/19 inhibitor, is being evaluated as a single agent for the treatment of patients with LR-MDS who have exhausted available treatment options. RVU120 has shown promising clinical safety and efficacy data already, as well as a strong preclinical and mechanistic rationale.
Treatment with RVU120 will be given to patients for at least 8 complete cycles. The primary end point of the study is to evaluate the safety and efficacy of RVU120, including to achieve hematologic improvement in the form of an erythroid response. Secondary end points include independence from red blood cell transfusions, improvement in hemoglobin levels, quality of life, disease progression, and analysis of specific gene mutations.
Eligible patients must be 18 years of age or older with a diagnosis of de novo MDS per WHO 2022 criteria, confirmed during screening.2 They should have very low, low, or intermediate-risk MDS (IPSS-R score ≤ 3.5) and may have del(5q) with up to 1 additional abnormality, excluding monosomy 7, del(7q), and TP53 mutations. Symptomatic anemia must be documented over a 16-week baseline period, with a hemoglobin mean of less than 10 g/dL or evidence of 3 or more red blood cell transfusions during this time.
Patients must have no approved MDS therapy options, should be either erythropoiesis-stimulating agent (ESA)-exposed and refractory/intolerant, or ESA-naive with serum erythropoietin >200 U/L; and luspatercept (Reblozyl)- or lenalidomide (Revlimid)-exposed and refractory/intolerant, or naive but ineligible. Additionally, patients should have an ECOG performance status of 0 to 2 and be off anticancer treatment for at least 2 weeks or 5 half-lives.
There are 4 planned phase 2 studies of RVU120 scheduled to begin in 2024, and REMARK represents the third. Treatment in both the RIVER-52 (NCT06268574) and RIVER-81 (NCT06191263) studies in acute myeloid leukemia have already begun.1 The fourth, the POTAMI-61 study (NCT06397313), will evaluate RVU120 as a monotherapy and in a combination for the treatment of patients with myelofibrosis, and is expected to begin soon.
