|View printer-friendly version|
Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Data Presentations in Frontline Non-Hodgkin Lymphoma at ASH 2015
December 7, 2015 at 4:31 PM EST
-Updated Phase 2 Data Evaluating ADCETRIS in Combination with RCHOP Chemotherapy in Frontline CD30-Expressing High Risk DLBCL Demonstrate an 84 Percent Objective Response Rate with a 76 Percent Complete Remission Rate-
-Updated Phase 1 Data Evaluating ADCETRIS in Combination with CHP Chemotherapy in Frontline Mature T-Cell Lymphoma Demonstrate a Three-Year Overall Survival Rate of 80 Percent, with Estimated Median Progression-Free Survival Not Yet Reached-
“There is a significant need to improve frontline treatment options in
aggressive non-Hodgkin lymphomas. In particular, newly diagnosed
patients with high-intermediate and high-risk DLBCL and MTCL have
estimated three-year progression-free survival rates of approximately 55
percent and 30 percent, respectively,” said
ADCETRIS is currently not approved for the treatment of frontline DLBCL and MTCL. For more information about the clinical trials, including enrolling centers, visit www.clinicaltrials.gov.
Brentuximab Vedotin with RCHOP as Frontline Therapy in Patients with
High-Intermediate/High-Risk Diffuse Large B-Cell Lymphoma (DLBCL):
Results from an Ongoing Phase 2 Study (Abstract #814, oral
Updated interim results were reported from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with the standard of care regimen consisting of rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) in frontline high-intermediate and high-risk DLBCL. Patients were randomized to receive standard dose RCHOP with either 1.2 milligrams per kilogram (mg/kg) or 1.8 mg/kg of ADCETRIS. The trial was designed to assess antitumor activity and the safety profile of ADCETRIS plus RCHOP in these patients. Exploratory endpoints included CD30 expression measured by immunohistochemistry (IHC) testing and the relationship between CD30 expression and response.
Data were reported from 51 frontline DLBCL patients with a median age of
67 years. Seventy-one percent of patients in the trial had stage IV
disease, 37 percent were considered high-risk and 63 percent were
considered high-intermediate risk. Key findings presented by
Based on these data, the phase 2 trial has been amended to add a randomized cohort exploring the activity and safety of ADCETRIS plus RCHP (without vincristine) versus RCHOP in frontline patients with CD30-expressing high-intermediate or high-risk DLBCL. Separately, a randomized phase 2 trial is also ongoing evaluating rituximab and bendamustine with or without ADCETRIS in relapsed or refractory DLBCL.
Frontline Treatment of CD30+ Peripheral T-cell Lymphomas with
Brentuximab Vedotin in Combination with CHP: 3-Year Durability and
Survival Follow-up (Abstract #1537, poster presentation on
Data were reported from 26 frontline MTCL patients who received the combination regimen of ADCETRIS plus cyclophosphamide, doxorubicin and prednisone (CHP). Patients who achieved at least a partial remission with combination therapy were eligible to receive continued single-agent ADCETRIS treatment. The median age of patients was 56 years. Nineteen patients (73 percent) had a subtype of MTCL called systemic anaplastic large cell lymphoma (sALCL), including 16 patients (62 percent) with anaplastic lymphoma kinase (ALK) negative disease, which is typically associated with a poor prognosis. Seven patients had a diagnosis of other types of MTCL. The majority of patients had advanced stage disease and were considered high risk.
Updated key findings based on a median observation time of 38.7 months from first dose of therapy include:
A global phase 3 study called ECHELON-2 is currently enrolling patients. The ECHELON-2 trial is a randomized, double-blind, placebo-controlled, multi-center trial designed to investigate A+CHP versus CHOP as frontline therapy in patients with CD30-positive MTCL. Approximately 450 patients (approximately 225 patients per treatment arm) will be randomized to receive A+CHP or CHOP every three weeks for six to eight cycles.
ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including the phase 3 ALCANZA trial and two additional phase 3 studies, ECHELON-1 in frontline classical HL and ECHELON-2 in frontline mature T-cell lymphomas, as well as trials in many additional types of CD30-expressing malignancies, including B-cell lymphomas.
ADCETRIS 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 for intravenous injection has received approval from the
ADCETRIS was granted conditional marketing authorization by the
ADCETRIS (brentuximab vedotin) U.S. Important Safety Information
Warnings and Precautions
Most Common Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients with relapsed classical HL and sALCL in two uncontrolled single-arm 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.
ADCETRIS was studied in 329 patients with classical HL at high risk of relapse or progression post-auto-HSCT in a placebo-controlled randomized trial. The most common adverse reactions (≥20%) in the ADCETRIS-treatment arm (167 patients), regardless of causality, were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.
Use in Specific Populations:
For additional Important Safety Information, including Boxed WARNING, please see the full Prescribing Information for ADCETRIS at http://www.seattlegenetics.com/pdf/adcetris_USPI.pdf.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to our future clinical
trials, potential future uses of ADCETRIS and our goal to establish
ADCETRIS as the foundation of therapy for a broad array of
CD30-expressing lymphomas. 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 risks
of adverse events associated with ADCETRIS use, negative or unexpected
ADCETRIS clinical trial results even after promising results in earlier
company and investigator-sponsored trials, and adverse regulatory
actions affecting ADCETRIS. More information about the risks and
uncertainties faced by