Adcetris may greatly benefit patients with cutaneous T-cell lymphoma (CTLC) who received prior systemic or radiation therapy, according to Phase 3 clinical trial results recently announced by Takeda Pharmaceutical Company and Seattle Genetics. The study met its primary endpoint, with Adcetris (bretuximab vedotin) showing a highly significant statistical improvement in objective response lasting at least four months compared to investigator’s choice standard therapies.
ALCANZA, as the trial is known, received scientific advice from the European Medicines Agency (EMA), meant to improve the trial design, and Special Protocol Assessment from the U.S. Food and Drug Administration (FDA), meaning that the study’s questions were appropriate for a potential drug approval.
“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, PhD, president and chief executive oficer of Seattle Genetics, said in a press release. “We anticipate reporting more complete ALCANZA data at the ASH [American Society of Hematology] 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 randomized, open-label, international and multicenter study was designed to assess the efficacy of Adcetris, which targets and kills CD30-positive cells, versus physician’s choice standard therapies (methotrexate or bexarotene) in patients with CD30-expressing CTCL, including those with primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF). Patients with pcALCL had at least one prior systemic radiation therapy, whereas those with MF had at least one prior systemic therapy. (Adcetris is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in about 50 percent of CTCL patients.)
The study included 131 patients who received Adcetris every three weeks, versus investigator’s choice, for up to a year. Adcetris was found to significantly increase an objective response of at least four months (ORR4) in patients treated with it, compared to the control group. In fact, 56.3 percent of patients in the Adcetris group achieved an objective response that lasted longer than four months, versus 12.5 percent in those given investigator’s choice.
Key secondary endpoints, such as progression-free survival, complete response rate, and reduction in the burden of symptoms during treatment, were also significantly improved in the Adcetris group versus control group.
“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,” said Dirk Huebner, MD, executive medical director, oncology therapeutic area unit, Takeda Pharmaceutical Company.
Adcetris is already approved by the FDA to treat Hodgkin lymphoma patients whose disease has progressed after autologous stem cell transplant or, for those who cannot undergo a transplant, after two prior chemotherapy treatments. It is also approved to treat a rare lymphoma known as systemic anaplastic large cell lymphoma (ALCL) in patients who failed at one prior chemotherapy regimen.