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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

Authors :
Thomas Pabst
Norbert Vey
Lionel Adès
Ulrike Bacher
Mario Bargetzi
Samson Fung
Gianluca Gaidano
Domenica Gandini
Anna Hultberg
Amy Johnson
Xuewen Ma
Rouven Müller
Kerri Nottage
Cristina Papayannidis
Christian Recher
Carsten Riether
Priya Shah
Jeffrey Tryon
Liang Xiu
Adrian F. Ochsenbein
Source :
Haematologica, Vol 108, Iss 7 (2023)
Publication Year :
2023
Publisher :
Ferrata Storti Foundation, 2023.

Abstract

Cusatuzumab is a high-affinity, anti-CD70 monoclonal antibody under investigation in acute myeloid leukemia (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. The primary objective in phase I was to determine the recommended phase II dose (RP2D) of cusatuzumab plus azacitidine. The primary objective in phase II was efficacy at the RP2D (selected as 10 mg/kg). Thirty-eight patients were enrolled: 12 in phase I (three per dose level; four with European LeukemiaNet 2017 adverse risk) and 26 in phase II (21 with adverse risk). An 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 an objective response among the 29 patients in phase I and phase II treated at the RP2D. At a median follow-up of 10.9 months, median duration of first response was 4.5 months and median overall survival was 11.5 months. The 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.

Details

Language :
English
ISSN :
03906078 and 15928721
Volume :
108
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Haematologica
Publication Type :
Academic Journal
Accession number :
edsdoj.44a72b022e1b4366bad1fca7a93513e4
Document Type :
article
Full Text :
https://doi.org/10.3324/haematol.2022.281563