Seattle Genetics, Inc. (Nasdaq: SGEN) today announced that results from two ongoing investigator-sponsored phase II clinical trials of ADCETRIS (brentuximab vedotin) in patients with relapsed cutaneous T-cell lymphoma (CTCL) were presented at the 54
American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS has not been approved for use in the treatment of CTCL.
Brentuximab Vedotin Demonstrates Significant Clinical Activity in Relapsed or Refractory Mycosis Fungoides with Variable CD30 Expression (Abstract #797)
The ongoing phase II clinical trial is enrolling CTCL patients with mycosis fungoides (MF) or Sezary syndrome. Twenty patients have been enrolled to date with a median of six prior systemic therapies. The primary endpoint of the trial is clinical response rate. Secondary endpoints include correlation of clinical response with CD30 expression levels, duration of response and safety. The study was led by principle investigator Dr. Youn H. Kim from Stanford University School of Medicine in Stanford, CA, and was presented in an oral session. Key findings include:
Results of a Phase II Trial of Brentuximab Vedotin (SGN-35) for CD30+ Cutaneous T-Cell Lymphomas and Lymphoproliferative Disorders (Abstract #3688)
- Fourteen of 20 patients (70 percent) achieved an objective response across all stages of disease, including Stage IB, Stage IIB and Stage IVA/B. At the time of analysis, 14 patients had a partial response, one patient had stable disease and four patients had progressive disease. One patient was not evaluable for response.
- CD30 expression on lymphoid cells in biopsies of skin lesions was measured by immunohistochemistry (IHC) and patients were divided into three groups: those with less than 10 percent expression (seven patients), 10 percent to 50 percent expression (10 patients) and greater than 50 percent expression (three patients). Clinical activity was observed in all three groups.
- The most common related adverse events of any grade were peripheral neuropathy (70 percent), fatigue (60 percent), decreased appetite (30 percent) and nausea (25 percent).
- The most common Grade 3 or 4 related adverse events were rash (three patients) and neutropenia (two patients).
Data were presented from a phase II investigator-sponsored trial evaluating the use of ADCETRIS in CD30-positive CTCL patients, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) or MF. The ongoing study is being conducted by Dr. Madeleine Duvic from The University of Texas MD Anderson Cancer Center in Houston, TX. Among 54 patients enrolled to date, 46 patients were evaluable at the time of analysis. The primary endpoint of the trial is to evaluate the safety and efficacy of ADCETRIS in CD30-positive CTCL. The key findings include:
- Thirty-one of 46 patients (67 percent) achieved an objective response, including 19 of 19 (100 percent) with LyP and/or pcALCL and 12 of 27 (44 percent) with MF.
- The most common adverse events were peripheral neuropathy (44 percent), fatigue (30 percent), skin rash (26 percent), diarrhea (22 percent), nausea (18 percent) and myalgia (18 percent).
- The most common Grade 3 adverse events were neutropenia (three patients), elevated liver function tests (two patients), nausea (two patients) and deep vein thrombosis (two patients).
Seattle Genetics and Millennium: The Takeda Oncology Company have initiated the ALCANZA trial, a randomized phase III clinical trial of ADCETRIS for relapsed CD30-positive CTCL patients. The trial is assessing ADCETRIS versus investigator’s choice of methotrexate or bexarotene in patients with CD30-positive CTCL, including those with pcALCL or MF. The primary endpoint of the study is overall response rate lasting at least four months. Approximately 124 patients will be enrolled in the pivotal trial. The ALCANZA trial is being conducted under a Special Protocol Assessment agreement from the U.S. Food and Drug Administration (FDA). The study also received European Medicines Agency scientific advice.