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

• Published in: Cancer 2022-03, Vol.128 (5), p.1004-1014
• Main Authors: Leupin, Nicolas, Zinzani, Pier Luigi, Morschhauser, Franck, Dalle, Stéphane, Maerevoet, Marie, Michot, Jean‐Marie, Ribrag, Vincent, Offner, Fritz, Beylot‐Barry, Marie, Moins‐Teisserenc, Hélène, Zwaenepoel, Karen, Winne, Koen, Battistella, Maxime, Hultberg, Anna, Gandini, Domenica, Moshir, Mahan, Jacobs, Julie, Delahaye, Tim, Khan, Aitzaz, Zabrocki, Piotr, Silence, Karen, Rompaey, Luc, Borg, Christophe, Motta, Giovanna, Melle, Federica, Calleri, Angelica, Pauwels, Patrick, Haard, Hans, Pileri, Stefano, Bagot, Martine
• Format: Article
• Language: English
• Subjects: Adverse events; Antibodies, Monoclonal - adverse effects; Anticancer properties; Antineoplastic Agents - therapeutic use; Antitumor activity; Asthenia; CD27 antigen; CD27 Ligand; CD70; CD70 antigen; clinical trial; cusatuzumab; cutaneous T‐cell lymphoma (CTCL); Dosage; Drug dosages; Fever; Health services; Humans; Immunogenicity; Life Sciences; Lymphoma; Lymphoma, T-Cell, Cutaneous - drug therapy; Monoclonal antibodies; Neoplasm Recurrence, Local - pathology; Oncology; Patients; Pharmacokinetics; Response rates; Skin Neoplasms - drug therapy; T-cell lymphoma; translational; Treatment Outcome; Vasculitis
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.34005

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. Cusatuzumab, a monoclonal antibody targeting CD70, is well tolerated and shows dose‐dependent evidence of antitumor activity in a heavily pretreated patient population with cutaneous T‐cell lymphoma. The overall response rate was 23% with increased efficacy in patients with Sézary syndrome, warranting further clinical development.