An anti-CD30 monoclonal antibody called brentuximab vedotin demonstrated in a randomized phase III study a highly statistically significant improvement in rate of objective response lasting at least 4 months.
monoclonal antibody called brentuximab vedotin (Adcetris) demonstrated in a randomized phase III study a highly statistically significant improvement in rate of objective response lasting at least 4 months (ORR4).
The randomized trial, which received a Special Protocol Assessment (SPA) from the US Food and Drug Administration (FDA) and scientific advice from the European Medicines Agency (EMA), compared the use of single-agent brentuximab vedotin to a control arm of investigator’s choice of standard therapies (methotrexate or bexarotene [Targretin]). The trial included 131 patients with CD30-expressing CTCL who received prior systemic or radiation therapy. Brentuximab vedotin is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on skin lesions in approximately 50% of patients with CTCL.
“Cutaneous T-cell lymphoma is a debilitating, disfiguring and painful disease, and there is a significant need for additional effective treatment options with meaningful durable responses. This is the first Phase 3 randomized trial in CTCL versus an active control to read out, and we are thrilled to have successfully demonstrated the positive impact of using Adcetris for patients enrolled in this study,” said Clay Siegall, PhD, President and Chief Executive Officer of Seattle Genetics, in a news release. “We anticipate reporting more complete ALCANZA data at the ASH annual meeting in December and intend to submit a supplemental Biologics License Application to the FDA in the first half of 2017 for approval in this setting.”
The results of the ALCANZA trial demonstrated the ORR4 was 56.3% in the brentuximab vedotin arm compared to 12.5% in the control arm. The key secondary endpoints, including complete response rate (CRR), progression-free survival (PFS), and reduction in the burden of symptoms during treatment, were all highly statistically significant in favor of the brentuximab vedotin arm. In addition, this agent was found to have a manageable safety profile.
Patients in this study received brentuximab vedotin every 3 weeks versus investigator’s choice for up to approximately 1 year. The international multicenter trial was conducted in North and South America, Europe, and Australia. The agent has already received orphan drug designation from the FDA for the treatment of mycosis fungoides (MF), which is the most common type of CTCL.
CTCL is the most common type of cutaneous lymphoma, according to the Cutaneous Lymphoma Foundation. Progression from limited skin involvement may be accompanied by tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood, and internal organs. The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation, and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30% to 45% objective response rates, with low complete response rates.