Phase III Trial Planned in Front-line Mature T-Cell Lymphomas-
SAN FRANCISCO, CA, USA I January 26, 2012 I Seattle Genetics, Inc. (Nasdaq:SGEN) and Millennium: The Takeda Oncology Company today announced interim results from 32 patients treated to date in a phase I clinical trial of ADCETRIS (brentuximab vedotin) administered in combination with or sequentially with chemotherapy for the treatment of newly diagnosed systemic anaplastic large cell lymphoma (sALCL) and other CD30-positive mature T-cell lymphoma patients. The data are being presented at the T-Cell Lymphoma Forum being held January 26-28, 2012 in San Francisco, CA. ADCETRIS is not approved for use in front-line mature T-cell lymphoma.
In the phase I trial, newly diagnosed patients are enrolled to one of two regimens evaluating ADCETRIS administered either sequentially with CHOP(1) or concurrently with CH-P, which removes vincristine from the regimen:
The sequential treatment regimen comprises two cycles of single-agent ADCETRIS every three weeks at 1.8 milligrams per kilogram (mg/kg) followed by six cycles of CHOP. Patients who achieve at least a partial remission (PR) after completing the six cycles of CHOP are eligible to receive continued single-agent ADCETRIS at 1.8 mg/kg for up to an additional eight 3-week cycles.
The concurrent treatment regimen comprises six cycles of ADCETRIS every three weeks in combination with CH-P. Patients who achieve at least a PR after completing the six cycles of combination therapy are eligible to receive continued single-agent ADCETRIS for up to an additional ten 3-week cycles.
Data were reported from 32 previously untreated patients, including 12 who received the sequential regimen and 20 who received the concurrent regimen. Thirty patients had sALCL, one patient had peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and one patient had human T-cell lymphotropic virus (HTLV)-1 associated T-cell lymphoma. Key findings, which will be presented by Dr. Michelle Fanale from The University of Texas MD Anderson Cancer Center, include:
The recommended dose of ADCETRIS in combination with CH-P is 1.8 mg/kg every three weeks.
Across all regimens, the most common adverse events regardless of severity or relationship to study drug were nausea (38 percent), fatigue (25 percent) and peripheral sensory neuropathy (25 percent). Grade 3 or higher adverse events regardless of relationship to study drug were anemia (6 percent), fatigue (6 percent), peripheral edema (6 percent) and white blood cell count decrease (6 percent).
All 12 patients (100 percent) treated with the sequential regimen achieved an objective response after two cycles of single-agent ADCETRIS, including four patients (33 percent) with a complete remission (CR) and eight patients (67 percent) with a PR. All 12 evaluable patients had sALCL. At the time of data analysis, six of these 12 patients had completed six subsequent cycles of CHOP and were evaluable for response. Of these six evaluable patients, four patients (67 percent) achieved a CR and two patients (33 percent) achieved a PR. Five remaining patients were not yet evaluable for response. One patient discontinued treatment during CHOP chemotherapy due to progressive disease, after achieving a PR with two cycles of ADCETRIS.
Among 20 patients treated with the concurrent regimen, all five patients (100 percent) who had completed the full course of six cycles of multi-agent induction treatment and were evaluable for response at the time of data analysis achieved a CR. All five evaluable patients had sALCL. The remaining 15 patients were not yet evaluable for response.
“The front-line regimen for aggressive T-cell lymphomas, including systemic ALCL, has not been improved upon since CHOP was introduced decades ago, and more than half of these patients will relapse,” said Dr. Michelle Fanale, Assistant Professor in the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “The interim data from this phase I clinical trial suggest that ADCETRIS has the potential to play an important role in advancing the treatment of newly diagnosed T-cell lymphoma patients, and continued investigation of ADCETRIS in these patients is warranted.”
The primary endpoints of the trial are dose-limiting toxicities, safety and tolerability of ADCETRIS when combined or used sequentially with multi-agent front-line chemotherapy regimens. The secondary endpoints are investigator assessment of response, progression-free survival (PFS) and overall survival (OS). The original clinical trial protocol included only sALCL patients, but was recently expanded to include patients with other subtypes of CD30-positive mature T- and NK-cell lymphomas. The median age of patients across all treatment arms was 58 years. Enrollment is ongoing in this phase I, open-label, multi-center trial.
A phase III clinical trial of ADCETRIS in CD30-positive mature T-cell lymphoma patients, including sALCL, is planned to compare PFS in patients receiving ADCETRIS in combination with CH-P to patients receiving CHOP alone.
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.
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.
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 is not approved for use outside the United States. The marketing authorization application for ADCETRIS in relapsed or refractory Hodgkin lymphoma and systemic ALCL, filed by Takeda Global Research & Development Centre (Europe), was accepted by the European Medicines Agency for review in June 2011.
About T-Cell Lymphomas
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. 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, 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 www.seattlegenetics.com.
About Millennium
Millennium: The Takeda Oncology Company , a leading biopharmaceutical company based in Cambridge, Mass., markets a first-in-class proteasome inhibitor in the US, and has a robust clinical development pipeline of global 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 and Takeda are available through their respective websites, http://www.millennium.com and http://www.takeda.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.
Adverse Reactions:
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.
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.
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 the featured clinical trials 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, 2011 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.
1) CHOP: cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine) and prednisone
Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=50147330&lang=en
SOURCE: Seattle Genetics, Inc.
Post Views: 53
Phase III Trial Planned in Front-line Mature T-Cell Lymphomas-
SAN FRANCISCO, CA, USA I January 26, 2012 I Seattle Genetics, Inc. (Nasdaq:SGEN) and Millennium: The Takeda Oncology Company today announced interim results from 32 patients treated to date in a phase I clinical trial of ADCETRIS (brentuximab vedotin) administered in combination with or sequentially with chemotherapy for the treatment of newly diagnosed systemic anaplastic large cell lymphoma (sALCL) and other CD30-positive mature T-cell lymphoma patients. The data are being presented at the T-Cell Lymphoma Forum being held January 26-28, 2012 in San Francisco, CA. ADCETRIS is not approved for use in front-line mature T-cell lymphoma.
In the phase I trial, newly diagnosed patients are enrolled to one of two regimens evaluating ADCETRIS administered either sequentially with CHOP(1) or concurrently with CH-P, which removes vincristine from the regimen:
The sequential treatment regimen comprises two cycles of single-agent ADCETRIS every three weeks at 1.8 milligrams per kilogram (mg/kg) followed by six cycles of CHOP. Patients who achieve at least a partial remission (PR) after completing the six cycles of CHOP are eligible to receive continued single-agent ADCETRIS at 1.8 mg/kg for up to an additional eight 3-week cycles.
The concurrent treatment regimen comprises six cycles of ADCETRIS every three weeks in combination with CH-P. Patients who achieve at least a PR after completing the six cycles of combination therapy are eligible to receive continued single-agent ADCETRIS for up to an additional ten 3-week cycles.
Data were reported from 32 previously untreated patients, including 12 who received the sequential regimen and 20 who received the concurrent regimen. Thirty patients had sALCL, one patient had peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and one patient had human T-cell lymphotropic virus (HTLV)-1 associated T-cell lymphoma. Key findings, which will be presented by Dr. Michelle Fanale from The University of Texas MD Anderson Cancer Center, include:
The recommended dose of ADCETRIS in combination with CH-P is 1.8 mg/kg every three weeks.
Across all regimens, the most common adverse events regardless of severity or relationship to study drug were nausea (38 percent), fatigue (25 percent) and peripheral sensory neuropathy (25 percent). Grade 3 or higher adverse events regardless of relationship to study drug were anemia (6 percent), fatigue (6 percent), peripheral edema (6 percent) and white blood cell count decrease (6 percent).
All 12 patients (100 percent) treated with the sequential regimen achieved an objective response after two cycles of single-agent ADCETRIS, including four patients (33 percent) with a complete remission (CR) and eight patients (67 percent) with a PR. All 12 evaluable patients had sALCL. At the time of data analysis, six of these 12 patients had completed six subsequent cycles of CHOP and were evaluable for response. Of these six evaluable patients, four patients (67 percent) achieved a CR and two patients (33 percent) achieved a PR. Five remaining patients were not yet evaluable for response. One patient discontinued treatment during CHOP chemotherapy due to progressive disease, after achieving a PR with two cycles of ADCETRIS.
Among 20 patients treated with the concurrent regimen, all five patients (100 percent) who had completed the full course of six cycles of multi-agent induction treatment and were evaluable for response at the time of data analysis achieved a CR. All five evaluable patients had sALCL. The remaining 15 patients were not yet evaluable for response.
“The front-line regimen for aggressive T-cell lymphomas, including systemic ALCL, has not been improved upon since CHOP was introduced decades ago, and more than half of these patients will relapse,” said Dr. Michelle Fanale, Assistant Professor in the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “The interim data from this phase I clinical trial suggest that ADCETRIS has the potential to play an important role in advancing the treatment of newly diagnosed T-cell lymphoma patients, and continued investigation of ADCETRIS in these patients is warranted.”
The primary endpoints of the trial are dose-limiting toxicities, safety and tolerability of ADCETRIS when combined or used sequentially with multi-agent front-line chemotherapy regimens. The secondary endpoints are investigator assessment of response, progression-free survival (PFS) and overall survival (OS). The original clinical trial protocol included only sALCL patients, but was recently expanded to include patients with other subtypes of CD30-positive mature T- and NK-cell lymphomas. The median age of patients across all treatment arms was 58 years. Enrollment is ongoing in this phase I, open-label, multi-center trial.
A phase III clinical trial of ADCETRIS in CD30-positive mature T-cell lymphoma patients, including sALCL, is planned to compare PFS in patients receiving ADCETRIS in combination with CH-P to patients receiving CHOP alone.
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.
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.
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 is not approved for use outside the United States. The marketing authorization application for ADCETRIS in relapsed or refractory Hodgkin lymphoma and systemic ALCL, filed by Takeda Global Research & Development Centre (Europe), was accepted by the European Medicines Agency for review in June 2011.
About T-Cell Lymphomas
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. 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, 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 www.seattlegenetics.com.
About Millennium
Millennium: The Takeda Oncology Company , a leading biopharmaceutical company based in Cambridge, Mass., markets a first-in-class proteasome inhibitor in the US, and has a robust clinical development pipeline of global 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 and Takeda are available through their respective websites, http://www.millennium.com and http://www.takeda.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.
Adverse Reactions:
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.
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.
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 the featured clinical trials 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, 2011 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.
1) CHOP: cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine) and prednisone
Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=50147330&lang=en
SOURCE: Seattle Genetics, Inc.
Post Views: 53
