Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy.

Cusatuzumab is a high-affinity, anti-CD70 monoclonal antibody under investigation in AML. This two-part, open-label, multicenter, phase I/II trial evaluated cusatuzumab plus azacitidine in patients with newly diagnosed AML ineligible for intensive chemotherapy. Patients received a single dose of cusatuzumab at one of four dose levels (1, 3, 10, or 20 mg/kg), 14 days before starting combination therapy. In phase I dose-escalation, cusatuzumab was then administered on days 3 and 17, in combination with azacitidine (75 mg/m2) on days 1-7, every 28 days. Primary objective in phase I was to determine the recommended phase II dose (RP2D) of cusatuzumab plus azacitidine. Phase II primary objective was efficacy at the RP2D (selected as 10 mg/kg). Thirty-eight patients enrolled: 12 in phase I (three per dose level; four with ELN adverse risk) and 26 in phase II (21 with adverse risk). Objective response (≥ partial remission) was achieved by 19/38 patients (including 8/26 in phase II); 14/38 achieved complete remission. Eleven patients (37.9%) achieved objective response among the 29 patients in phase I and phase II treated at the RP2D. At median follow-up of 10.9 months, median duration of first response was 4.5 months and median overall survival was 11.5 months. Most common treatment-emergent adverse events were infections (84.2%) and hematologic toxicities (78.9%). Seven patients (18.4%) reported infusion-related reactions, including two with grade 3 events. Thus, cusatuzumab/azacitidine appears generally well tolerated and shows preliminary efficacy in this setting. Investigation of cusatuzumab combined with current standard-of-care therapy, comprising venetoclax and azacitidine, is ongoing.