CD25-targeted antibody-drug conjugate camidanlumab tesirine for relapsed or refractory classical Hodgkin lymphoma

Abstract

Classic Hodgkin lymphoma (cHL) accounts for more than 90% of HL in developed countries. Although the current combined modality therapy make it have a high cure rate, the prognosis for heavily pretreated patients with relapsed or refractory (R/R) cHL remains poor. A novel antibody-drug conjugate (ADC), named camidanlumab tesirine (ADCT-301, Cami), is currently being evaluated for its efficacy and safety in R/R cHL. The primary objective of this review is to examine the current pharmacological properties of camidanlumab tesirine as well as its clinical antitumor activity and safety. Camidanlumab tesirine comprises a human IgG1 anti-CD25 monoclonal antibody HuMax®-TAC, conjugated to a pyrrolobenzodiazepine dimer toxin. Once it bound to CD25-expressing cells, camidanlumab tesirine is internalized by cells and delivers SG3199, then SG3199 irreversibly binds to DNA and forms DNA interstrand crosslinks, ultimately leading to cell death. In the phase 1 study, patients with R/R cHL who received camidanlumab tesirine had an overall response rate (ORR) of 71% and a complete response rate (CRR) of 42%. Additionally, the recommended doses provided in R/R cHL were determined to be 30 and 45 μg/kg. The pivotal phase 2 trial showed significant antitumor activity of camidanlumab tesirine in heavily pretreated R/R cHL patients who failed brentuximab vedotin and programmed death-1 blockade: ORR was 70.1% and CRR was 33.3%, and the median duration of response was 13.7 months. Adverse events such as fatigue, maculopapular rash, and anemia were frequently observed following administration of camidanlumab tesirine. Moreover, camidanlumab tesirine may cause Guillain-Barré syndrome or polyradiculopathy.

Keywords: Antibody drug conjugate; CD25; Camidanlumab tesirine; Classic Hodgkin lymphoma; Relapsed or refractory.