Phase III Trial Is Assessing Combination of Tamibarotene, Azacitidine in Patients with MDS

An ongoing phase III trial is underway assessing the addition of tamibarotene to azacitidine versus azacitidine alone in newly diagnosed adults with higher-risk myelodysplastic syndromes (MDS). Amy DeZern, MD, of Johns Hopkins University, described the study in progress during the Society of Hematologic Oncology (SOHO) Annual Meeting.

Nearly a third (30%) of patients with higher-risk MDS have an overexpression of the RARA gene. Tamibarotene is an oral selective RARα agonist that may have potential clinical benefit in patients with RARA-positive higher-risk MDS, irrespective of mutation or cytogenetic risk.

A previous study of tamibarotene in patients with RARA-positive, relapsed/refractory higher-risk MDS demonstrated improved blood counts, myeloid differentiation, and reduced bone marrow blasts following treatment. In another study, the combination of tamibarotene and azacitidine resulted in a complete remission (CR)/CR with incomplete hematologic recovery rate of 61% in RARA-positive newly diagnosed unfit patients with acute myeloid leukemia, and a majority of these patients achieved or maintained transfusion independence following this treatment regimen.

Based on these and other prior studies, researchers are conducting the global, randomized, double-blind, placebo-controlled SELECT-MDS-1 trial to compare outcomes for patients treated with tamibarotene and azacitidine versus azacitidine plus placebo.

The researchers plan to enroll 190 patients with RARA-positive newly diagnosed higher-risk MDS who will be randomized 2:1 to receive azacitidine 75 mg/m² intravenously or subcutaneously on days one through seven with or without tamibarotene 6 mg orally twice daily on days eight to 28 of each 28-day cycle.

Eligible patients will include those with a Revised International Prognostic Scoring System risk category of very high, high, or intermediate and a blast count greater than 5% at baseline. Previously treated patients with higher-risk MDS will be excluded from the trial.

The main outcome is response per the modified International Working Group MDS criteria, with secondary objectives including overall response rate, event-free and overall survival, transfusion independence, and safety.

Reference

DeZern A, Fenaux P, Deeren D, et al. SELECT-MDS-1 Trial in progress: a phase 3 randomized, double-blind, placebo-controlled study of tamibarotene/azacitidine versus placebo/azacitidine in newly diagnosed adult patients selected for RARA-positive higher-risk MDS. Abstract #MDS-110. Presented at the 2022 Society of Hematologic Oncology (SOHO) Annual Meeting, September 28-October 1, 2022.