|Seattle Genetics Reports Data from Phase I Trial of ADCETRIS® (Brentuximab Vedotin) in Front-line Mature T-Cell Lymphomas (MTCL)|
-100 Percent Objective Response Rate, Including 88 Percent Complete Remissions, in Newly Diagnosed MTCL Patients Treated with ADCETRIS in Combination with CHP Chemotherapy-
-Data Support Planned Phase III Trial in Front-line MTCL, Including Systemic Anaplastic Large Cell Lymphoma and Other Types of Peripheral T-cell Lymphomas-
In the phase I trial, newly diagnosed patients received six cycles of ADCETRIS every three weeks in combination with cyclophosphamide, doxorubicin and prednisone (CHP). This regimen removes vincristine (Oncovin) from CHOP, the standard treatment in this setting. Patients who achieved at least a partial remission after completing six cycles of combination therapy were eligible to receive continued single-agent ADCETRIS for up to ten additional 3-week cycles. The primary endpoints of the trial included defining maximum tolerated dose of ADCETRIS in combination with CHP and evaluating safety. The secondary endpoints were investigator assessment of response, progression-free survival and overall survival.
After completing combination therapy, 26 of 26 patients (100 percent) treated with ADCETRIS plus CHP had an objective response, including 23 patients (88 percent) with a complete remission. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET (positron emission tomography) evaluation.
“The standard front-line regimen for patients with mature T-cell
lymphomas is a combination chemotherapy regimen, CHOP, that has
demonstrated complete remission rates of 39 to 53 percent, with a 5-year
overall survival rate of less than 50 percent,” said
Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy as Front-line Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell Lymphomas (Abstract #60)
Data were reported from 26 previously untreated patients who received the combination regimen of ADCETRIS plus CHP. Nineteen patients had sALCL, and seven patients had a diagnosis of another mature T- or NK-cell lymphoma. The median age of patients was 56 years. Key findings, which were highlighted in an oral presentation by Dr. Fanale, include:
“These data provide strong rationale for our planned phase III clinical
trial to evaluate ADCETRIS plus CHP compared to CHOP in front-line
patients with mature T-cell lymphomas,” said
A phase III clinical trial of ADCETRIS in CD30-positive MTCL patients is planned to compare progression-free survival in patients receiving ADCETRIS in combination with CHP (A+CHP) to patients receiving CHOP alone. The trial is expected to begin by late 2012 or early 2013.
ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.
ADCETRIS was granted accelerated approval by the
ADCETRIS was granted conditional marketing authorization by the
About T-Cell Lymphomas
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. Non-Hodgkin lymphomas are broadly
divided into two major groups: B-cell lymphomas, which develop from
abnormal B-lymphocytes, and T-cell lymphomas, which develop from
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS in the featured indication. Actual results or
developments may differ materially from those projected or implied in
these forward-looking statements. Factors that may cause such a
difference include the inability to show sufficient activity in future
clinical trials studying such indication and the risk of adverse events
as ADCETRIS advances in such clinical trials. In addition, data from our
clinical trials, including our pivotal trials which were the basis for