Cusatuzumab combined with venetoclax with or without azacitidine in unfit patients with newly diagnosed acute myeloid leukemia: phase Ib ELEVATE study

Abstract

Cusatuzumab is a monoclonal antibody that binds with high affinity to CD70, a cell surface protein overexpressed on CD34+ acute myeloid leukemia (AML) progenitors and leukemia stem cells. This phase Ib study assessed the safety, tolerability and efficacy of adding cusatuzumab to standard-of-care azacitidine and venetoclax (CVA) or a cusatuzumab and venetoclax (CV) doublet regimen in patients newly diagnosed with AML who were ineligible for intensive chemotherapy. Cusatuzumab 20 mg/kg was administered intravenously on days 3 and 17 of 28-day cycles combined with standard dosing of venetoclax ± azacitidine. Overall, 44 patients were treated with CVA. Common hematologic treatment-emergent adverse events (TEAEs) were neutropenia (77.3%), thrombocytopenia (77.3%) and anemia (45.5%); non-hematologic TEAEs included nausea (45.5%), diarrhea (43.2%), constipation (40.9%), fatigue (36.4%) and vomiting (31.8%). Grade ≥3 infectious complications included febrile neutropenia (38.6%), sepsis (36.4%) and pneumonia (9.1%). The overall composite response rate (complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi]) was 77.3% (CR, 47.7%; CRh, 20.5%; CRi, 9.1%). Among CR/CRi responders, 53% achieved negative measurable residual disease by multiparameter flow cytometry. Median overall survival was 12.0 months (95% confidence interval: 8.7-NE) months. Sixteen patients were treated with CV and had similar safety but less favorable responses and survival than those treated with CVA. These results support further development of CVA for the treatment of AML (clinicaltrials.gov identifier: NCT04150887).