STIMULUS-MDS1 Trial Compares Sabatolimab Plus HMAs Versus Placebo in Higher-Risk MDS

While sabatolimab showed a manageable safety profile in patients with higher-risk myelodysplastic syndromes (MDS), adding sabatolimab to hypomethylating agents (HMAs) did not significantly improve complete response rates (CRR) or progression-free survival (PFS), according to a phase II study published in The Lancet Hematology.

Led by Amer Zeidan, MBBS, MHS, of the Yale University Cancer Center, the trial compared the efficacy and safety of sabatolimab plus a HMA, versus placebo plus an HMA, in patients with untreated, higher-risk MDS.

A total of 127 patients from 54 investigational sites were randomized into two groups: the intravenous sabatolimab group (n=65), or the placebo plus an HMA (n=62) group. The former group received intravenous sabatolimab at 400 mg on days eight and 22, while the latter group received either intravenous decitabine at 20 mg/m² on days one to five, or intravenous or subcutaneous azacitidine at 75 mg/m² on days one to seven or days one to five and eight and nine.

The primary endpoints included CRR and PFS. CR was achieved in 14 patients (22%) in the sabatolimab group, versus 11 patients (18%) in the placebo group (P=0.77). The median PFS was 11.1 months in the sabatolimab group, versus 8.5 months in the placebo group (P=0.1022).

The most common adverse events (AEs) in either group included neutropenia, thrombocytopenia, constipation, diarrhea, anemia, febrile neutropenia, and leukopenia. One patient in the sabatolimab group developed a serious potential treatment-related immune-mediated AE, and another patient died due to pneumonitis.

“A randomized phase III trial is ongoing to assess the potential benefit of sabatolimab plus azacitidine on overall survival in this setting,” the researchers wrote.

Reference

Zeidan A, Ando K, Rauzy O, et al. Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haemato. 2023. doi.org/10.1016/S2352-3026(23)00333-2