Seattle Genetics Announces Initiation of Phase 1/2 Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with …

BOTHELL, Wash.--(BUSINESS WIRE)--

Seattle Genetics, Inc. (SGEN) today announced the initiation of a phase 1/2 clinical trial evaluating ADCETRIS (brentuximab vedotin) in combination with bendamustine for patients with Hodgkin lymphoma (HL) after first relapse. The multi-phase study is divided into two cohorts to determine the recommended dosing level and tolerability of combination use and to assess the complete remission rate associated with ADCETRIS in combination with bendamustine. Seattle Genetics is the leader in the field of antibody-drug conjugates (ADCs) and ADCETRIS is an ADC directed to CD30, a defining marker of classical HL. ADCETRIS is not approved for salvage HL patients who are deemed eligible for autologous stem cell transplant (ASCT).

One of the key goals of our broad ADCETRIS clinical development program is to evaluate its use in earlier lines of HL therapy. This trial will assess the ability of ADCETRIS in combination with bendamustine to induce durable complete remissions in second-line treatment of HL patients prior to transplant, said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. In this treatment setting, single-agent bendamustine has been shown to induce a high rate of remissions with limited durability. Data from an investigator-sponsored trial with single-agent ADCETRIS demonstrated encouraging activity and tolerability in this setting. This trial is designed to determine if the combination can result in durable complete remissions, potentially increasing the number of patients eligible to receive a transplant.

This phase 1/2 single-arm, open-label clinical trial will evaluate the efficacy and tolerability of ADCETRIS in combination with bendamustine in HL patients after first relapse. Patients will be eligible to receive up to six cycles of ADCETRIS in combination with bendamustine followed by additional single-agent ADCETRIS for up to a total of 16 cycles. As a part of the trial design, after patients receive ADCETRIS plus bendamustine combination therapy, they have the option to pause therapy to receive an ASCT and then resume treatment with single-agent ADCETRIS as consolidation. Bendamustine is an alkylating agent used in the treatment of chronic lymphocytic leukemias and lymphomas. The primary endpoint of the phase 1 cohort is to determine the recommended dosing level of bendamustine in combination with ADCETRIS as well as the safety and tolerability of the combination. The primary endpoint of the phase 2 cohort is to assess the complete remission rate. Key secondary endpoints include best response, duration of response and progression-free survival. The study is expected to enroll up to 50 patients at multiple centers in the United States.

At the 54th American Society of Hematology (ASH) Annual Meeting and Exposition held December 8-11, 2012 in Atlanta, GA, encouraging data were presented from an abstract titled Brentuximab Vedotin as a First Line Salvage Therapy in Relapsed/Refractory HL (Abstract #3699). The investigator-sponsored trial was conducted to evaluate ADCETRIS as a salvage therapy for HL. Fourteen patients were evaluated for response and safety and all had relapsed or refractory HL after initial therapy with chemotherapy regimens or a combination of chemotherapy with or without consolidative radiation treatment.

Of the 14 evaluable patients, 12 patients (85.7 percent) had an objective response rate, including seven (50 percent) complete remissions and five (35.7 percent) partial remissions. The most common Grade 1 or 2 adverse events were peripheral sensory neuropathy (42.9 percent), acneiform rash (35.7 percent), AST elevation (28.6 percent) and fatigue (28.6 percent). Grade 3 adverse events were rash acneiform (7.1 percent) and urinary tract infection (7.1 percent), and there were no Grade 4 adverse events. The abstract can be found at http://www.hematology.org.

More information about the phase 1/2 trial of ADCETRIS in combination with bendamustine, including enrolling centers, is available by visiting http://www.clinicaltrials.gov.

About ADCETRIS

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 FDA in August 2011 and approval with conditions by Health Canada in February 2013 for two indications: (1) the treatment of patients with HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.

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Seattle Genetics Announces Initiation of Phase 1/2 Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with ...