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

by Selleckchem | Mar 07 2023

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.

Comments：

It seems that cusatuzumab, a high-affinity, anti-CD70 monoclonal antibody, was evaluated in a phase I/II trial in combination with azacitidine for the treatment of newly diagnosed AML in patients who are ineligible for intensive chemotherapy. The trial aimed to determine the recommended phase II dose of cusatuzumab plus azacitidine in phase I and to evaluate the efficacy of the combination therapy at the recommended dose in phase II.

The trial enrolled 38 patients, with 12 in phase I and 26 in phase II. The primary objective in phase I was to determine the recommended phase II dose, which was selected as 10 mg/kg. The primary objective in phase II was efficacy at the recommended phase II dose. The results showed that objective response (≥ partial remission) was achieved by 19/38 patients, including 8/26 in phase II, and 14/38 achieved complete remission.

At the median follow-up of 10.9 months, the median duration of the first response was 4.5 months, and the median overall survival was 11.5 months. The most common treatment-emergent adverse events were infections (84.2%) and hematologic toxicities (78.9%). Infusion-related reactions were reported in 7 patients (18.4%), including 2 with grade 3 events.

The findings suggest that cusatuzumab/azacitidine appears generally well-tolerated and shows preliminary efficacy in the treatment of newly diagnosed AML in patients who are ineligible for intensive chemotherapy. Ongoing investigation of cusatuzumab in combination with current standard-of-care therapy comprising venetoclax and azacitidine may provide further insight into the potential use of this therapy in AML treatment.