A phase 3 study of brentuximab vedotin (Adcetris, Takeda/Seattle Genetics) in patients with cutaneous T-cell lymphoma (CTCL) has met its primary endpoint, demonstrating a significant improvement in the objective response rate compared with that of standard therapies. The responses with brentuximab lasted at least four months (ORR4).
The randomized trial compared the use of single-agent brentuximab with a control arm consisting of the investigator’s choice of standard therapies (methotrexate or bexarotene) in 131 patients with CD30-expressing CTCL who had received systemic or radiation therapy.
Brentuximab is an antibody–drug conjugate (ADC) directed at CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL. Brentuximab consists of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.
In the ALCANZA trial, 131 subjects received brentuximab or the investigator’s choice of therapy every three weeks for up to approximately one year. Treatment with brentuximab resulted in a significant improvement in the ORR4 compared with the control arm (P <0.0001). The ORR4 was 56.3% in the brentuximab arm compared with 12.5% in the control arm. Key secondary endpoints, including the complete response rate, progression-free survival, and the reduction in the burden of symptoms during treatment, were all significantly in favor of the brentuximab arm.
Brentuximab for intravenous injection has received FDA approval for three indications: 1) the treatment of patients with classical Hodgkin’s lymphoma after the failure of autologous hematopoietic stem-cell transplantation (auto-HSCT) or after the failure of at least two multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates; 2) the treatment of classical Hodgkin’s lymphoma patients at high risk of relapse or progression as post–auto-HSCT consolidation; and 3) the treatment of patients with systemic anaplastic large-cell lymphoma (sALCL) after the failure of at least one multi-agent chemotherapy regimen. Brentuximab is not approved for the treatment of CTCL.
Source: Takeda; August 1, 2016.