MDS-420: Sabatolimab Plus Hypomethylating Agents (HMAs) in Patients with High-/Very High-risk Myelodysplastic Syndrome (HR/vHR-MDS) and Newly Diagnosed Acute Myeloid Leukemia (ND-AML): Subgroup Analysis of a Phase 1 Study

Context: Sabatolimab (MBG453) is an investigational immuno-myeloid therapy targeting TIM-3, an immune regulator expressed on immune and myeloid leukemic cells and blasts, but not on normal hematopoietic stem cells. Early phase 1b study (NCT03066648) results showed sabatolimab+HMA treatment had promising and durable activity in MDS/AML. Objective: To further explore safety/tolerability and efficacy in patient subgroups, as well as biomarkers with sabatolimab+HMA. Design: Study design/eligibility criteria have been reported. HMA-naive patients with HR/vHR-MDS and ND-AML and ineligible for intensive chemotherapy received sabatolimab (1–2 infusions/month) + decitabine or azacitidine. Primary objectives: safety/tolerability. Secondary objectives: PK and preliminary efficacy. Data cutoff was 22 September 2020; updated data will be presented. Results: Of 89 patients with HR/vHR-MDS (n=41) and ND-AML (n=48), 36 (40%) had sabatolimab dose interruption, 1 (1%) had dose reduction, 2 (2%) had dose interruption and reduction, 5 (6%) discontinued, and 3 (3%) had dose interruption and discontinued. Four discontinuations were due to AEs and 4 due to death. Twenty-two patients had grade 4 neutropenia/thrombocytopenia at baseline: 4 (18%) had dose interruption, 2 (9%) discontinued, and 1 (5%) had dose interruption and discontinued. In analyses of remission rates (CR+mCR/CRi+PR) by baseline factors, response was independent of bone marrow blast burden in patients with HR/vHR-MDS or ND-AML. Remission rates were similar in patients age ≥75 and 65–74 years: 50% (6/12) and 65% (11/17) with HR/vHR-MDS and 42% (8/19) for both groups with ND-AML. Response durability in patients age ≥75 and 65–74 years was encouraging: an estimated 83% and 86%, respectively, with HR/vHR-MDS remained in remission after 6 months. In patients with TP53 mutation or ≥1 mutation conferring European LeukemiaNet (ELN) high risk, remission rates were 55% (6/11; 4/6 in remission >200 days) and 59% (13/22; 8/13 in remission >200 days), respectively, for HR/vHR-MDS. Durability and remission rates for ND-AML will be presented. Biomarker analyses identified differential expression of IL-1β in sabatolimab+HMA responders vs nonresponders; expression levels were inversely correlated with remission. Conclusions: Sabatolimab+HMA showed favorable tolerability in MDS/AML, including in patients with grade 4 cytopenias at baseline. Promising remission rates were observed across patient subgroups. This supports development of sabatolimab+HMA in the STIMULUS trial program of MDS/AML.