Lymphoma Drug Significantly Improves Response Rate in Phase 3 Trial

A phase 3 trial of brentuximab vedotin (Adcetris) for patients with cutaneous T cell lymphoma (CTCL) met its primary endpoint, demonstrating a highly statistically significant improvement in the rate of objective response lasting at least 4 months (ORR4).

Adcetris is an antibody-drug conjugate, comprised of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, called monomethyl auristatin E (MMAE).

The randomized phase 3 trial called ALCANZA received a Special Protocol Assessment (SPA) from the FDA, and scientific advice from the European Medicines Agency (EMA). The goal of the study was to compare the use of Adcetris to a control arm of standard therapies methotrexate or bexarotene in 131 CD30-expressing CTCL patients who received prior systemic or radiation therapy.

The results of the study showed a highly statistically significant improvement in the ORR4 using Adcetris, compared with the control arm assessed by an independent review committee (p-value <0.0001). In the Adcetris arm, the ORR4 was 56.3% compared with 12.5% in the control arm.

The key secondary endpoints included the complete response rate, progression-free survival, and reduction in the burden of symptoms during treatment. This was found to be highly statistically significant in favor of the Adcetris arm.

“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,” said Clay Siegall, PhD, president and chief executive officer of Seattle Genetics. “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. 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.”

For the safety profile for Adcetris, it was found to be generally consistent with existing prescribing information. An abstract for the data presentation will be submitted at the American Society of Hematology (ASH) annual meeting in California.

“These remarkable, clinically meaningful results from the completed ALCANZA trial represent an important milestone for the Adcetris program,” said Dirk Huebner, MD, executive medical director, Oncology Therapeutic Area Unit at Takeda Pharmaceutical Company. “If this new indication is approved by regulatory authorities, Adcetris may offer a novel treatment option for CTCL patients. We are excited by the data, which showed a significant improvement in the primary endpoint of ORR4 and all key secondary endpoints, along with manageable safety profile. This outcome further establishes out commitment to patients living with CD-30 expressing disease, and we look forward to sharing these data with regulatory authorities globally.”