- Preliminary data reported today at the ESMO 2012 Congress (European Society for Medical Oncology) -
Cambridge, Mass., and Bothell, Wash., October 1, 2012 - Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502), and Seattle Genetics, Inc. (Nasdaq: SGEN), today announced preliminary data from one arm of a three arm phase I, open-label, multicenter study designed to determine the safety and activity of sequential and combination treatment approaches of brentuximab vedotin with CHOP or CH-P chemotherapy in newly diagnosed patients with CD30-positive mature T- and NK- cell lymphomas. Data were presented from one arm, which evaluates brentuximab vedotin in sequence with CHOP in patients with newly diagnosed systemic anaplastic large cell lymphoma (sALCL), a subtype of mature T- and NK cell lymphomas. The data were reported during an oral presentation at the ESMO 2012 Congress (European Society for Medical Oncology) being held September 28 - October 2, 2012 in Vienna, Austria.
Brentuximab vedotin is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of sALCL. Data from the other arms of the study evaluating administration of brentuximab vedotin with CH-P are expected to be presented during 2012.
"The preliminary data from the sequential treatment arm of this phase I study show that side effects were manageable and there are also some encouraging data on activity," said Michelle Fanale, M.D., University of Texas MD Anderson Cancer Center, Houston, TX. "We look forward to reporting additional data from the combination arms of the study at an upcoming medical congress."
Sequential Therapy with Brentuximab Vedotin in Newly Diagnosed Patients with Systemic Anaplastic Large Cell Lymphoma
The oral presentation featured data from Arm 1 of the study, which evaluated treatment with 1.8 milligrams per kilogram of single-agent brentuximab vedotin for two cycles prior to six cycles of CHOP. Patients who achieved a complete remission (CR) or partial remission (PR) following CHOP were eligible to continue single-agent brentuximab vedotin for up to eight cycles. The primary endpoints for Arm 1 are safety and tolerability. The secondary endpoint is investigator assessment of response using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). The median age of enrolled patients was 62 years (range, 23‑81). Among the 13 patients with newly diagnosed sALCL, ten had anaplastic lymphoma kinase (ALK)-negative disease and three had ALK-positive disease.
The companies plan to initiate a phase III clinical trial in patients with mature T-cell lymphomas evaluating brentuximab vedotin in combination with CH-P compared to CHOP in late 2012 to early 2013.
Data, presented by Dr. Fanale, included:
- The most common (≥30 percent of total patients) adverse events (AEs), regardless of severity, were nausea (77 percent), peripheral sensory neuropathy (77 percent), vomiting (54 percent), constipation (46 percent) and fatigue (46 percent)
- The most common (≥10 percent of total patient) AEs of Grade 3 or higher were anemia, constipation, fatigue, peripheral sensory neuropathy and febrile neutropenia, each occurring in 15 percent of patients
- Of the 13 evaluable patients on Arm 1 of the study, 100 percent achieved an objective response following the first two cycles of treatment with single-agent brentuximab vedotin, including five CRs and eight PRs
- After eight cycles of sequential therapy, including two cycles of brentuximab vedotin followed by six cycles of CHOP, 11 patients had an objective response, including eight CRs and three PRs
- Objective responses were generally maintained in patients treated with single-agent brentuximab vedotin following CHOP, including seven of nine evaluable patients with CRs at Cycle 12 and five of five evaluable patients with CRs at Cycle 16
Details of the oral presentation are as follows:
- Monday, October 1; 11:15 - 11:30 AM Central European Time (CET)
- Abstract #1063O
- Oral presentation in Hall K
- First author: Michelle Fanale, M.D., The University of Texas M. D. Anderson Cancer Center
Data on brentuximab vedotin was also described in the following poster session:
- Peripheral blood stem cell (PBSC) mobilization and engraftment after brentuximab vedotin treatment in anaplastic large cell lymphoma
- Sunday, September 30; 1:00 - 2:00 PM CET
- Abstract #1083P
- Hall XL
- First author: Andrei Shustov, M.D., University of Washington School of Medicine
About Brentuximab Vedotin
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.
Brentuximab vedotin is not approved for use outside the United States. The marketing authorization application for brentuximab vedotin in relapsed or refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research & Development Centre (Europe), 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.
Millennium and Seattle Genetics are jointly developing brentuximab vedotin. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize brentuximab vedotin in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for brentuximab vedotin on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs.
About Anaplastic Large Cell Lymphoma
ALCL is a type of aggressive T-cell lymphoma, comprising about 3 percent of all non-Hodgkin lymphomas (NHL) in adults and between 10 and 30 percent of all NHL in children. There are two distinct forms/types of ALCL, including primary cutaneous ALCL and systemic ALCL (sALCL). sALCL is a clinically aggressive, systemic lymphoma that primarily involves lymph nodes.
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, in the United States 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 Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer. The FDA granted accelerated approval of ADCETRIS in August 2011 for two indications. ADCETRIS is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has three other clinical-stage ADC programs: SGN-75, ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Abbott, Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys, an affiliate of Astellas, and Genmab. More information can be found at http://www.seattlegenetics.com.
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
- Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Treating physicians should monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
- Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be immediately and permanently discontinued and appropriate medical management instituted.
- Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation. Prolonged (≥1 week) severe neutropenia can occur with ADCETRIS.
- Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these patients should be monitored closely and appropriate measures taken.
- Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
- Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer appropriate medical therapy.
- Use in pregnancy: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus.
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 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.
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com.
For Seattle Genetics:
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of ADCETRIS and initiation of future clinical trials. 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 inability to show sufficient activity in future clinical trials, including the phase III clinical trial evaluating brentuximab vedotin in combination with CH-P compared to CHOP for patients with newly diagnosed CD30-positive mature T-cell lymphomas. In addition, data from our clinical trials, including our pivotal trials which were the basis for FDA accelerated approval, may not necessarily be indicative of subsequent clinical trial results. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's 10-Q for the quarter ended June 30, 2012 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Editor's Note: This press release is also available under the Media section of the Company's website at: www.millennium.com/InTheNews.aspx.
Seattle Genetics, Inc.
CHOP - cyclophosphamide, doxorubicin, oncovin and prednisone