CTCL patients with prior systemic/radiation therapy: New data from ALCANZA, a phase III trial with brentuximab vedotin

“CTCL patients expressing CD30 are incurable and more treatment options are needed”, said Professor H Miles Prince AM, Director of Molecular Oncology and Cancer Immunology at the Centre for Blood Cell Therapies, Peter MacCallum Cancer Centre, University of Melbourne, in Australia. He is one of the investigators for the ALCANZA trial.

A press release was recently published by Takeda Pharmaceutical Company Limited and Seattle Genetics Inc. announcing clinical data from a Phase 3 ALCANZA randomized trial evaluating the use of single-agent brentuximab vedotin (ADCETRIS) compared to a control arm of investigator’s choice of standard therapies (methotrexate or bexarotene) in patients (n=131) with CD30-expressing cutaneous T-Cell Lymphoma (CTCL) who received prior systemic or radiation therapy.  “It is the first randomized trial of patients with advanced stage disease against an active comparator arm. There was a study a few years ago of denileukin diftitox but it was compared to placebo. The most common other drugs used in such population are methotrexate, bexarotene, alpha interferon and the histone deacetylase inhibitors-vorinostat and romidepsin” commented Miles Prince. The primary endpoint, rate of objective response lasting at least four months ORR4) was “novel because it captures the proportion of patients who respond initially but progress early” specified Miles Prince. As stated in the press release, the trial demonstrated statistically significant improvements in the primary and in all secondary endpoints (i.e., complete response rate, progression free survival) along with a manageable safety profile.  

The press release summarises the key findings of the ALCANZA (NCT01578499) trial which are as follows:

• Treatment with brentuximab vedotin has shown statistically significant improvement in the ORR4 versus the control arm as assessed by an independent review committee (p-value <0.0001).
• The ORR4 was 56.3% in the brentuximab vedotin arm compared to 12.5% in the control arm.
• The key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment, were all statistically significant for the brentuximab vedotin arm.
• The safety profile associated with brentuximab vedotin from the ALCANZA trial was consistent with the existing prescribing information.

Conclusions

The results of the phase III randomized ALCANZA trial have shown that brentuximab vedotin should be a potential treatment option for CTCL patients.

Abstract

An abstract has be submitted for data presentation at the American Society of Hematology (ASH) annual meeting, December 3-6, 2016, in San Diego, California.

Press Release

Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, of Takeda Pharmaceutical Company said “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.”

Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics said “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.”

The press release article can be found here.