– Safety and Response Data Support Currently Enrolling Phase III Trial Evaluating ADCETRIS plus AVD Chemotherapy in Patients with Newly Diagnosed Hodgkin Lymphoma –
– ADCETRIS in Combination with AVD Chemotherapy Showed a 96 Percent Complete Remission Rate in Patients with Newly Diagnosed Advanced Hodgkin Lymphoma –
Atlanta, GA – December 10, 2012 –Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited (TSE:4502) today announced results from a phase I clinical trial of ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the treatment of patients with newly diagnosed advanced stage Hodgkin lymphoma (HL). These data were presented at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. ADCETRIS is currently not approved for use in the treatment of newly diagnosed HL.
In this open-label, multicenter trial, cohorts of patients received escalating doses of ADCETRIS ranging from 0.6 mg/kg to 1.2 mg/kg every two weeks concomitantly with ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) or a dose of 1.2 mg/kg every two weeks concomitantly with AVD, which removes bleomycin from the regimen. The trial was designed to establish the safety profile and maximum tolerated dose when adding ADCETRIS to ABVD or AVD. Antitumor activity was assessed as a secondary endpoint.
Pulmonary toxicity was seen in the ADCETRIS plus ABVD arm of this study. The concomitant administration of ADCETRIS and bleomycin is contraindicated. ADCETRIS combined with AVD was generally well tolerated. To date, no pulmonary toxicity events have been observed in the ADCETRIS plus AVD cohorts.
Results from the ADCETRIS plus AVD arm of this phase I clinical trial showed 24 of 25 patients (96 percent) had a complete remission (CR), while 21 of 22 (95 percent) of patients treated with ADCETRIS plus ABVD had a CR.
“For decades researchers have strived to find ways to improve the front-line HL treatment strategy by enhancing the activity of traditional chemotherapy regimens while reducing toxicities and long-term side effects of such regimens,” said Stephen Ansell, M.D., Ph.D., Medical Oncologist. “An unmet medical need remains for patients in the front-line HL setting. With a complete response rate of 96 percent and a generally manageable safety profile, data from this trial support further evaluation of ADCETRIS administered concomitantly with AVD.”
Front-line Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma (Abstract #798)
Fifty-one patients were enrolled in the phase I study and 47 were evaluable for response at trial completion. The 47 evaluable patients included 25 in the ADCETRIS plus AVD cohorts and 22 in the ADCETRIS plus ABVD cohorts. All patients were previously untreated with Stage IIA bulky disease or Stage IIB-IV Hodgkin lymphoma. The median age of patients across all cohorts of the trial was 33 years. Key findings, which were highlighted in an oral presentation by Dr. Stephen Ansell, included:
- No dose-limiting toxicity was observed at the maximum planned dose of ADCETRIS (1.2 milligrams per kilogram [mg/kg] every two weeks).
- The most common adverse events (>50 percent) noted in the ABVD and AVD cohorts, respectively, were nausea (72 percent, 85 percent), neutropenia (80 percent, 77 percent), peripheral sensory neuropathy (72 percent, 73 percent), vomiting (60 percent, 42 percent) and fatigue (44 percent, 50 percent).
- Grade 3 or higher adverse events noted in the ABVD and AVD cohorts, respectively, were neutropenia (80 percent, 77 percent), anemia (20 percent, 12 percent), febrile neutropenia (20 percent, 8 percent) and pulmonary toxicity (24 percent, 0 percent).
- Among the 25 evaluable patients in the ADCETRIS plus AVD cohorts, 24 patients (96 percent) who completed front-line therapy on study achieved a CR and one patient (4 percent) experienced disease progression.
- Among the 22 evaluable patients in the ADCETRIS plus ABVD cohorts, 21 patients (95 percent) who completed front-line therapy on study achieved a CR. One patient was not evaluable for response due to adverse events.
Millennium and Seattle Genetics have initiated a phase III clinical trial in patients with newly diagnosed advanced stage HL. The randomized trial is comparing progression-free survival in patients receiving ADCETRIS in combination with AVD to patients receiving ABVD alone. For more information about the trial, please visit www.clinicaltrials.gov.
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 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 systemic anaplastic large cell lymphoma (sALCL).
ADCETRIS received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2011 for two indications: (1) 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 (2) 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.
Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. 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.
About Hodgkin Lymphoma
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 based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company’s research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, www.millennium.com.
About Takeda Pharmaceutical Company Limited
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate Website, www.takeda.com.