Seattle Genetics, Inc. has started phase I/II 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 programme 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 I/II 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 I 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 II 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 centres in the United States.

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 tumour 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: 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 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.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL): following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory sALCL.

ADCETRIS is being evaluated in more than 20 ongoing clinical trials across both corporate and investigator-sponsored studies. The trials are designed to broadly evaluate the potential of ADCETRIS in earlier lines of its approved indications as well as in many additional types of CD30-positive malignancies, including cutaneous T-cell lymphoma (CTCL), B-cell lymphomas and mature T-cell lymphomas (MTCL).

Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has US and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group is solely responsible for development costs.

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. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell generally expresses CD30.

Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer.