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Seattle Genetics Demonstrates Commitment to Improve Hodgkin Lymphoma (HL) Treatment Paradigm Through Multiple ADCETRIS® (Brentuximab Vedotin) Data Presentations at ASH 2015
December 7, 2015 at 10:31 AM EST
-Final Pivotal Trial Results in Relapsed/Refractory HL Demonstrate Durable Remissions Lasting More than Five Years After ADCETRIS Monotherapy-
-Data From Multiple Presentations Support Goal to Establish ADCETRIS
-ADCETRIS Being Evaluated Broadly in more than 45 HL Clinical Trials-
“For the past decade, we have been committed to improving the
therapeutic options for HL patients, and we have made tremendous
progress with ADCETRIS, which is now
ADCETRIS is currently not approved for the treatment of frontline HL or as combination therapy for HL.
Five-Year Survival Data Demonstrating Durable Responses from a
Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed
or Refractory Hodgkin Lymphoma (Abstract #2736, poster presentation on
A pivotal, single-arm trial, which supported the
Updated Efficacy and Safety Data from the AETHERA Trial of
Consolidation with Brentuximab Vedotin after Autologous Stem Cell
Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse
(Abstract #3172, poster presentation on
The phase 3 AETHERA clinical trial was designed to evaluate the
potential of single-agent ADCETRIS to extend progression-free survival
post-ASCT in patients with classical HL who were at high risk of relapse
or progression. Patients received ADCETRIS or placebo every three weeks
for up to approximately one year (16 cycles). A total of 329 HL patients
were enrolled, including 165 on the ADCETRIS arm and 164 on the placebo
arm. Based on these trial results, ADCETRIS was approved by the
Brentuximab Vedotin in Combination with Dacarbazine or Bendamustine
for Frontline Treatment of Hodgkin Lymphoma in Patients Aged 60 Years
and Above: Interim Results of a Multi-Cohort Phase 2 Study (Abstract
#587, oral presentation on
Interim results were presented from an ongoing phase 2 clinical trial
evaluating ADCETRIS in combination with dacarbazine or bendamustine
(Treanda) as frontline therapy for HL patients age 60 years or older.
ADCETRIS combination data were reported from 22 patients treated with
dacarbazine and 20 patients treated with bendamustine. The median age of
patients was 69 years in the dacarbazine combination arm and 75 years in
the bendamustine combination arm. At least 70 percent of patients in
each arm had stage III/IV disease at the time of diagnosis and the
majority were frail with multiple comorbidities. The data will be
highlighted in an oral presentation by
Combination data evaluating ADCETRIS and dacarbazine or bendamustine include:
Brentuximab Vedotin Plus Bendamustine: A Highly Active Salvage
Treatment Regimen for Patients with Relapsed or Refractory Hodgkin
Lymphoma (Abstract #3982, poster presentation on
Updated data were presented from an ongoing phase 1/2 single-arm, open-label clinical trial evaluating the efficacy and tolerability of ADCETRIS in combination with bendamustine in HL patients who had relapsed or were refractory to frontline therapy. The combination therapy was administered every three weeks, for up to six cycles, followed by additional treatment with single-agent ADCETRIS for up to a total of 16 cycles of therapy. After patients have received at least two cycles of combination therapy, they have the option to pause treatment to receive an ASCT and then resume treatment with single-agent ADCETRIS as consolidation. Current treatment options in this setting include salvage chemotherapy regimens that historically have resulted in variable complete remission rates of 19 to 60 percent and are associated with significant toxicities.
Data were reported from 55 patients with a median age of 36 years. The majority of patients (53 percent) had stage III/IV disease at the time of initial diagnosis, with 28 primary refractory patients (51 percent) and 27 relapsed patients (49 percent) after frontline therapy, primarily consisting of the chemotherapy regimen ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine). Updated data from this phase 1/2 trial include:
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
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS® (brentuximab vedotin).
ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
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.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.
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 including HL. 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