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

  • Haematologica. 2023 Jul 1;108(7):1793-1802. doi: 10.3324/haematol.2022.281563.
Thomas Pabst  1 ,  Norbert Vey  2 ,  Lionel Adès  3 ,  Ulrike Bacher  4 ,  Mario Bargetzi  5 ,  Samson Fung  6 ,  Gianluca Gaidano  7 ,  Domenica Gandini  8 ,  Anna Hultberg  8 ,  Amy Johnson  9 ,  Xuewen Ma  9 ,  Rouven Müller  10 ,  Kerri Nottage  11 ,  Cristina Papayannidis  12 ,  Christian Recher  13 ,  Carsten Riether  14 ,  Priya Shah  15 ,  Jeffrey Tryon  11 ,  Liang Xiu  11 ,  Adrian F Ochsenbein  14
Affiliations
  • 1. Department of Medical Oncology, University Hospital, Inselspital and University of Bern, Bern. [email protected].
  • 2. Hématologie Clinique, Institut Paoli-Calmettes, Marseille.
  • 3. Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris and Université Paris Cité, and Centre d'Investigation Clinique (INSERM CIC 1427), Paris.
  • 4. Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern.
  • 5. Division of Hematology and Transfusion Medicine, Kantonsspital Aarau, Aarau.
  • 6. Fung Consulting Healthcare and Life Sciences, Eching.
  • 7. Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Maggiore Hospital, Novara.
  • 8. argenx, Ghent.
  • 9. Janssen Research and Development, Spring House, PA.
  • 10. Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich.
  • 11. Janssen RD, Raritan, NJ.
  • 12. IRCCS, Azienda Ospedaliero Universitaria di Bologna, Istituto di Ematologia "L e A Seràgnoli", Bologna.
  • 13. Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Service d'Hématologie, Toulouse, France and Université Toulouse III Paul Sabatier, Toulouse.
  • 14. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of BioMedical Research (DBMR), University of Bern, Bern.
  • 15. Janssen RD, High Wycombe, Buckinghamshire.
PMID: 36779592 DOI: 10.3324/haematol.2022.281563
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.

Products