Cusatuzumab for treatment of CD70-positive relapsed or refractory cutaneous T-cell lymphoma

  • Cancer. 2022 Mar 1;128(5):1004-1014. doi: 10.1002/cncr.34005.
Nicolas Leupin  1 ,  Pier Luigi Zinzani  2  3 ,  Franck Morschhauser  4 ,  Stéphane Dalle  5 ,  Marie Maerevoet  6 ,  Jean-Marie Michot  7 ,  Vincent Ribrag  7 ,  Fritz Offner  8 ,  Marie Beylot-Barry  9 ,  Hélène Moins-Teisserenc  10 ,  Karen Zwaenepoel  11 ,  Koen de Winne  11 ,  Maxime Battistella  10 ,  Anna Hultberg  1 ,  Domenica Gandini  1 ,  Mahan Moshir  1 ,  Julie Jacobs  1 ,  Tim Delahaye  1 ,  Aitzaz Khan  1 ,  Piotr Zabrocki  1 ,  Karen Silence  1 ,  Luc van Rompaey  1 ,  Christophe Borg  12 ,  Giovanna Motta  13 ,  Federica Melle  13 ,  Angelica Calleri  13 ,  Patrick Pauwels  11 ,  Hans de Haard  1 ,  Stefano Pileri  13 ,  Martine Bagot  14
Affiliations
  • 1. Argenx, Zwijnaarde, Belgium.
  • 2. IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
  • 3. Istituto di Ematologia "Seràgnoli," Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università degli Studi, Bologna, Italy.
  • 4. Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Université de Lille, CHU Lille, EA 7365, Lille, France.
  • 5. Department of Dermatology, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
  • 6. Service Hématologie, Institut Jules Bordet, Brussels, Belgium.
  • 7. Gustave Roussy, Villejuif, France.
  • 8. University Hospital Gent, Gent, Belgium.
  • 9. Inserm U1053, Department of Dermatology, Centre Hospitalier, Bordeaux, France.
  • 10. Hôpital Saint Louis, Université de Paris, INSERM U1160, Paris, France.
  • 11. Department of Pathology, University Hospital Antwerp, Edegem, Belgium.
  • 12. Inserm U645, Centre Hospitalier Universitaire de Besançon, Besançon, France.
  • 13. Division of Hematopathology, European Institute of Oncology, IRCCS, Milan, Italy.
  • 14. Inserm U976, Hôpital Saint Louis, Université de Paris, Paris, France.
PMID: 34726773 DOI: 10.1002/cncr.34005
Abstract

Background: The clinical benefit of cusatuzumab, a CD70-directed monoclonal antibody with enhanced effector functions, was investigated in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

Methods: In this cohort expansion of the ARGX-110-1201 study, 27 patients with R/R CTCL received cusatuzumab at 1 (n = 11) or 5 mg/kg (n = 16) once every 3 weeks to investigate its safety, dose, and exploratory efficacy. The pharmacokinetics, immunogenicity, CD70 expression, and CD70/CD27 biology were also assessed.

Results: The most common adverse events included infusion-related reactions, pyrexia, and asthenia. Eighteen serious adverse events (grade 1-3) were reported in 11 patients; 1 of these (vasculitis) was considered drug-related. For 8 of the 11 patients receiving 1 mg/kg, anti-drug antibodies (ADAs) affected the minimal concentration, and this resulted in undetectable cusatuzumab concentrations at the end of treatment and, in some cases, a loss of response. This effect was greatly reduced in the patients receiving 5 mg/kg. The overall response rate was 23%; this included 1 complete response and 5 partial responses (PRs) in 26 of the 27 evaluable patients. In addition, 9 patients achieved stable disease. The mean duration on cusatuzumab was 5.2 months, and the median duration was 2.5 months. Patients with Sézary syndrome (SS) achieved a 60% PR rate with a dosage of 5 mg/kg and a 33% PR rate with a dosage of 1 mg/kg; this resulted in an overall response rate of 50% for patients with SS at both doses.

Conclusions: Cusatuzumab was well tolerated, and antitumor activity was observed at both 1 and 5 mg/kg in highly pretreated patients with R/R CTCL. The observed dose-dependent effect on exposure supports the use of 5 mg/kg for future development.

Keywords
CD70; clinical trial; cusatuzumab; cutaneous T-cell lymphoma (CTCL); translational.
Products