Seattle Genetics, Inc. (Nasdaq: SGEN) today announced that interim
results from an investigator-sponsored phase II clinical trial of
ADCETRIS (brentuximab vedotin) in patients with relapsed cutaneous
T-cell lymphoma (CTCL) were presented at the Society for Investigative
Dermatology annual meeting being held May 9-12, 2012 in Raleigh, NC.
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS
has not been approved for use in CTCL.
The trial enrolled CTCL patients with mycosis fungoides (MF) or Sezary
syndrome. At the time of data analysis, 17 patients had been enrolled,
including 16 with MF and one with Sezary syndrome. Patients had received
a median of six prior therapies, including a median of four 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,
progression-free survival and safety. The study is led by principal
investigator Dr. Youn H. Kim, Professor, Department of Dermatology, and
Director, Multidisciplinary Cutaneous Lymphoma Program at Stanford
University School of Medicine in Stanford, CA. Key findings include:
Twelve of 16 evaluable patients (75 percent) achieved a partial
remission. Three patients had stable disease and one patient had
progressive disease. One patient was not yet evaluable for response.
Median CD30 expression on lymphoid cells in biopsies of skin lesions
was 15 percent. Clinical activity was not dependent on CD30 expression
Sixty-eight percent of patients maintained response at week 25. Median
duration of response had not yet been reached.
Adverse events were mostly Grade 1 or 2, with the most common related
events being peripheral neuropathy (76 percent), fatigue (65 percent),
decreased appetite (30 percent) and generalized skin eruption (30
percent). The most common event of Grade 3 or higher was generalized
skin eruption (18 percent). One patient experienced Grade 4 peripheral
neuropathy. There was one patient death due to respiratory failure
presumably secondary to pneumonia.
This is the second data set reported with ADCETRIS in CTCL patients. At
the T-Cell Lymphoma Forum in January 2012, interim data were presented
from a phase II investigator-sponsored trial in CD30-positive CTCL
patients, including lymphomatoid papulosis, primary cutaneous anaplastic
large cell lymphoma (pcALCL) or MF. In the trial, which is being
conducted by Dr. Madeleine Duvic at The University of Texas MD Anderson
Cancer Center, 11 of 17 evaluable patients (65 percent) achieved an
objective response, including seven complete remissions (CRs) and four
partial remissions (PRs). The most common adverse events were Grade 1,
including diarrhea, chest tightness, alopecia, nausea, elevated liver
enzymes and peripheral neuropathy.
Seattle Genetics and Millennium: The Takeda Oncology Company recently
initiated a randomized phase III clinical trial of ADCETRIS for relapsed
CD30-positive CTCL patients. The trial will assess 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 4
months. Approximately 124 patients will be enrolled in the pivotal
trial. The phase III 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.
Lymphoma is a general term for a group of cancers that originate in the
lymphatic system. There are two major categories of lymphoma: Hodgkin
lymphoma and non-Hodgkin lymphoma. Cutaneous lymphomas are a category of
non-Hodgkin lymphomas that primarily involve the skin.