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

Autor: Leupin, Nicolas, Zinzani, Pier Luigi, Morschhauser, Franck, Dalle, Stephane, Maerevoet, Marie, Michot, Jean-Marie, Ribrag, Vincent, Offner, Fritz, Beylot-Barry, Marie, Moins-Teisserenc, Helene, Zwaenepoel, Karen, De Winne, Koen, Battistella, Maxime, Hultberg, Anna, Gandini, Domenica, Moshir, Mahan, Jacobs, Julie, Delahaye, Tim, Khan, Aitzaz, Zabrocki, Piotr, Silence, Karen, van Rompaey, Luc, Borg, Christophe, Motta, Giovanna, Melle, Federica, Calleri, Angelica, Pauwels, Patrick, de Haard, Hans, Pileri, Stefano, Bagot, Martine, de Winne, Koen
Rok vydání: 2021
Předmět:
Zdroj: Cancer: interdisciplinary international journal of the American Cancer Society
ISSN: 1097-0142
0008-543X
DOI: 10.1002/cncr.34005
Popis: 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 Sezary 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.
Databáze: OpenAIRE
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