Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited and Seattle Genetics, Inc. has started an international phase III clinical trial evaluating ADCETRIS (brentuximab vedotin) as part of a frontline combination chemotherapy regimen in patients with previously untreated advanced Hodgkin lymphoma (HL). The trial is being conducted under a Special Protocol Assessment (SPA) agreement from the US Food and Drug Administration (FDA) and the trial also received scientific advice from the European Medicines Agency (EMA).

ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL.

“Millennium is pleased to announce the initiation of the phase III trial of ADCETRIS in patients with previously untreated advanced Hodgkin lymphoma. This is a key step in our efforts to explore the potential of this targeted therapy as part of a frontline treatment regimen,” said Karen Ferrante, MD, chief medical officer, Millennium. “The trial is part of our ongoing development programme to explore patient populations that may benefit from treatment with ADCETRIS in earlier lines of therapy and in other CD30-expressing malignancies.”

“There have been no new therapies approved for patients with newly diagnosed HL in many decades, representing a significant need to identify additional treatment options in this setting,” said Thomas C Reynolds, MD, PhD, chief medical officer, Seattle Genetics. “We believe through this novel ADCETRIS-containing regimen we have the potential to redefine the treatment of frontline HL. This trial is also an important part of our development plan for ADCETRIS, and may serve as confirmatory to our US accelerated approval in relapsed HL and systemic anaplastic large cell lymphoma.”

The randomized, open-label, phase III trial will investigate ADCETRIS+AVD versus ABVD as frontline therapy in patients with advanced classical HL. The primary endpoint is modified progression free survival (mPFS) per independent review facility assessment using the Revised Response Criteria for malignant lymphoma. Secondary endpoints include overall survival (OS), complete remission (CR) and safety. The multi-center trial will be conducted in North America, Europe, Latin America and Asia. The study will enroll approximately 1,040 eligible patients (approximately 520 patients per treatment arm) who have histologically-confirmed diagnosis of Stage III or IV classical HL who have not been previously treated with systemic chemotherapy or radiotherapy.

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 received accelerated approval from the US Food and Drug Administration (FDA) in August 2011 for two indications: the treatment of patients with Hodgkin lymphoma 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 systemic anaplastic large cell lymphoma (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 is not approved for use outside the United States. The Marketing Authorization Application (MAA) for ADCETRIS in relapsed or refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research & Development Centre (Europe), Ltd., was accepted for review by the European Medicines Agency (EMA) in June 2011. In July 2012, the Committee for Medicinal Products for Human Use (CHMP) of the EMA issued a positive opinion for the conditional marketing authorization of brentuximab vedotin for two indications.

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 will be 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.

Millennium: The Takeda Oncology Company, a leading biopharmaceutical company mainly in research, development and commercialization activities are focused in oncology.

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