Seattle Genetics, Inc. (Nasdaq: SGEN) today announced results from a phase I clinical trial of ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the treatment of newly diagnosed mature T-cell lymphoma (MTCL) patients, including patients with systemic anaplastic large cell lymphoma (sALCL). The data were presented at the 54 th 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. ADCETRIS is not currently approved for use in the front-line treatment of MTCL. In the phase I trial, newly diagnosed patients received six cycles of ADCETRIS every three weeks in combination with cyclophosphamide, doxorubicin and prednisone (CHP). This regimen removes vincristine (Oncovin) from CHOP, the standard treatment in this setting. Patients who achieved at least a partial remission after completing six cycles of combination therapy were eligible to receive continued single-agent ADCETRIS for up to ten additional 3-week cycles. The primary endpoints of the trial included defining maximum tolerated dose of ADCETRIS in combination with CHP and evaluating safety. The secondary endpoints were investigator assessment of response, progression-free survival and overall survival. After completing combination therapy, 26 of 26 patients (100 percent) treated with ADCETRIS plus CHP had an objective response, including 23 patients (88 percent) with a complete remission. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET (positron emission tomography) evaluation. “The standard front-line regimen for patients with mature T-cell lymphomas is a combination chemotherapy regimen, CHOP, that has demonstrated complete remission rates of 39 to 53 percent, with a 5-year overall survival rate of less than 50 percent,” said Michelle Fanale, M.D., Associate Professor in the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “There is significant need to advance the treatment paradigm for newly diagnosed patients with these aggressive types of lymphoma. Data from this trial support further evaluation of ADCETRIS in the front-line treatment of patients with mature T-cell lymphomas.”
Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy as Front-line Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell Lymphomas (Abstract #60)Data were reported from 26 previously untreated patients who received the combination regimen of ADCETRIS plus CHP. Nineteen patients had sALCL, and seven patients had a diagnosis of another mature T- or NK-cell lymphoma. The median age of patients was 56 years. Key findings, which were highlighted in an oral presentation by Dr. Fanale, include:
- All 26 patients (100 percent) achieved an objective response after either completing six cycles of combination therapy or at the latest assessment for three patients who discontinued treatment prior to cycle six. Twenty-three patients (88 percent) achieved a complete remission and three patients (12 percent) achieved a partial remission.
- Among 19 sALCL patients, 19 (100 percent) achieved an objective response, including 16 (84 percent) with a complete remission.
- Among the seven non-sALCL patients, 100 percent achieved a complete remission with combination therapy, including two patients with PTCL – not otherwise specified (PTCL-NOS), two patients with angioimmunoblastic T-cell lymphoma, two patients with adult T-cell leukemia/ lymphoma and one patient with enteropathy-associated T-cell lymphoma.
- Median progression-free survival and median overall survival have not been reached with a median follow-up of nine months.
- Patients received a median of six cycles of CHP plus ADCETRIS and a median of six additional cycles of single-agent ADCETRIS.
- The maximum tolerated dose of ADCETRIS in combination with CHP was not exceeded at 1.8 milligrams per kilogram (mg/kg).
- The most common treatment-emergent adverse events of any grade regardless of relationship occurring in more than 30 percent of patients were nausea (62 percent), peripheral sensory neuropathy (62 percent), diarrhea (58 percent), fatigue (54 percent) and alopecia (46 percent).
- The most common Grade 3 or 4 treatment-emergent adverse events regardless of relationship included Grade 3 febrile neutropenia, peripheral sensory neuropathy, nausea and dyspnea and Grade 4 nausea and diarrhea.
A phase III clinical trial of ADCETRIS in CD30-positive MTCL patients is planned to compare progression-free survival in patients receiving ADCETRIS in combination with CHP (A+CHP) to patients receiving CHOP alone. The trial is expected to begin by late 2012 or early 2013.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 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 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 has not been approved for use in any front-line setting. 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): (1) following autologous stem cell transplant (ASCT), or (2) 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). See important safety information below. 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 is solely responsible for development costs.
About T-Cell LymphomasLymphoma 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. Non-Hodgkin lymphomas are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. The World Health Organization identifies 22 subtypes of mature T- and NK-cell neoplasms, including systemic ALCL which is an aggressive type of T-cell non-Hodgkin lymphoma that expresses CD30. Other mature T-cell lymphomas include PTCL, angioimmunoblastic T-cell lymphoma and adult T-cell lymphoma. 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, Agensys (an affiliate of Astellas), Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys and Genmab. More information can be found at www.seattlegenetics.com. U.S. Important Safety Information BOXED WARNING Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS. Contraindication: 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.
Drug Interactions: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 . Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of ADCETRIS in the featured indication. 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 studying such indication and the risk of adverse events as ADCETRIS advances in such clinical trials. 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 September 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.