Adcetris met its primary endpoint in a phase 3 trial for patients with T-cell lymphoma.
Patients with CD-30­—positive cutaneous T-cell lymphoma (CTCL) saw a significantly improved rate of response lasting at least four months on Adcetris (brentuximab vedotin), meeting the primary endpoint of the phase 3 ALCANZA trial.
In the trial, the rate of objective responses lasting four or more months was 56.3 percent in patients treated with Adcetris, compared with 12.5 percent in patients receiving investigator’s choice of standard therapies. The difference was highly statistically significant, according to Takeda and Seattle Genetics, the manufacturers of the antibody-drug conjugate.
“These remarkable, clinically meaningful results from the completed ALCANZA trial represent an important milestone for the Adcetris program. If this new indication is approved by regulatory authorities, Adcetris may offer a novel treatment option for CTCL patients,” Dirk Huebner, executive medical director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company, said in a statement.
“We are excited by the data, which showed a significant improvement in the primary endpoint of [the rate of object responses lasting more than four months] and all key secondary endpoints, along with a manageable safety profile. This outcome further establishes our commitment to patients living with CD30-expressing disease, and we look forward to sharing these data with regulatory authorities globally,” added Huebner.
The open-label phase 3 ALCANZA trial randomized 131 patients with CD30-expressing CTCL, including patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF). The international trial was conducted at 50 locations in North and South America, Europe and Australia. Patients with MF had to have received at least one prior systemic therapy and those with pcALCL were required to have prior radiation therapy or at least one systemic therapy.
The study randomized patients to single-agent Adcetris or physician’s choice of the standard treatments methotrexate or bexarotene. Adcetris was administered intravenously at 1.8 mg/kg once every three weeks and for up to 48 weeks (16 cycled). Methotrexate was dosed at 5 to 50 mg once weekly and bexarotene was administered orally at 300 mg/m2 once daily.
Beyond the primary endpoint of objective response rate lasting greater than months, secondary outcome measures included complete response rate, progression-free survival and reduction in the burden of symptoms during treatment.
“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,” Clay Siegall, president and CEO of Seattle Genetics, said in a statement. “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.”
Adcetris consists of the anti-CD30 monoclonal antibody SGN-30 conjugated to the cytotoxic agent monomethyl auristatin E (MMAE) via a valine-citrulline peptide linker. The treatment is internalized by CD30 expressing tumor cells, causing the release of MMAE into the cytosol through the enzymatic cleavage of the linker.
CD30 is expressed on skin lesions in approximately half of patients with CTCL, according to Takeda and Seattle Genetics’ statement. The FDA previously granted Adcetris an orphan drug designation for the treatment of patient with MF, and the European Commission (EC) has assigned the treatment an orphan drug designation for CTCL, including pcALCL and MF.
Adcetris is not currently approved by the FDA or EC for CTCL. In the United States and Europe, the drug has approved indications for Hodgkin lymphoma and systemic anaplastic large cell lymphoma.