- Interim Data Demonstrate 65 Percent Response Rate in Patients with Relapsed CTCL-
- Two Case Studies Provide First Report of Activity and Tolerability in PTCL-NOS Patients-
SAN FRANCISCO, CA, USA I January 26, 2012 I Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that interim results from an investigator-sponsored phase II clinical trial of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) were presented at the T-Cell Lymphoma Forum being held January 26-28, 2012 in San Francisco, CA. In addition, case studies were presented on two patients with relapsed peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) who were treated with ADCETRIS. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS is not approved for use in CTCL or PTCL-NOS.
Investigator-Sponsored Phase II Trial in CTCL
At the time of data analysis, 17 of 23 enrolled patients had received at least two doses of ADCETRIS and were evaluable for response. All patients had relapsed CD30-positive cutaneous lymphoproliferative disorders, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF). Patients treated in this trial receive 1.8 milligrams per kilogram (mg/kg) of ADCETRIS every three weeks for up to a maximum of eight doses. Patients who achieve partial remission or stable disease are eligible to receive an additional eight doses. Key findings, which were presented by Dr. Madeleine Duvic from The University of Texas MD Anderson Cancer Center, include:
Eleven of 17 evaluable patients (65 percent) achieved an objective response, including seven complete remissions (CRs) and four partial remissions (PRs). Six patients had stable disease. These investigator-assessed responses were observed in all three subtypes of CTCL.
The most common adverse events were Grade 1, including diarrhea, chest tightness, alopecia, nausea, elevated liver enzymes and peripheral neuropathy. ADCETRIS treatment was held in two patients with Grade 2 peripheral sensory neuropathy and in one patient with Grade 4 neutropenia and Grade 3 leukopenia. One patient died of sepsis after one dose of ADCETRIS.
Variable CD30 expression was observed in baseline lesions.
The clinical trial is ongoing with planned enrollment of 29 patients.
PTCL Case Studies
Data were also presented from case studies of two patients with relapsed CD30-positive PTCL-NOS who were enrolled in phase I trials of ADCETRIS. PTCL-NOS is associated with a poor prognosis and there is no well-established standard of care. Both patients were heavily pretreated, including prior autologous stem cell transplant. The first patient achieved a PR with progression-free survival of eight months and overall survival of 22 months. Adverse events considered related to ADCETRIS were Grade 2 sensory neuropathy in the fingertips and Grade 3 fatigue. The second patient achieved a CR which is still ongoing with a duration of more than 19 months. The patient had Grade 3 anemia and other Grade 1 adverse events, none of which were considered by the investigator to be related to ADCETRIS.
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: The Takeda Oncology Company 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 CTCL or PTCL-NOS.
ADCETRIS is not approved for use outside the United States. The marketing authorization application for ADCETRIS in relapsed or refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research & Development Centre (Europe), was accepted by the European Medicines Agency for review in June 2011.
Seattle Genetics and Millennium: The Takeda Oncology Company are planning a phase III clinical trial of ADCETRIS in CD30-positive CTCL patients to begin by mid-2012.
About CTCL
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. Cutaneous lymphomas are a category of non-Hodgkin lymphomas that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma that typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement is variable and may be accompanied by tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.
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.
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.
SOURCE: Seattle Genetics
Post Views: 68
- Interim Data Demonstrate 65 Percent Response Rate in Patients with Relapsed CTCL-
- Two Case Studies Provide First Report of Activity and Tolerability in PTCL-NOS Patients-
SAN FRANCISCO, CA, USA I January 26, 2012 I Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that interim results from an investigator-sponsored phase II clinical trial of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) were presented at the T-Cell Lymphoma Forum being held January 26-28, 2012 in San Francisco, CA. In addition, case studies were presented on two patients with relapsed peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) who were treated with ADCETRIS. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS is not approved for use in CTCL or PTCL-NOS.
Investigator-Sponsored Phase II Trial in CTCL
At the time of data analysis, 17 of 23 enrolled patients had received at least two doses of ADCETRIS and were evaluable for response. All patients had relapsed CD30-positive cutaneous lymphoproliferative disorders, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF). Patients treated in this trial receive 1.8 milligrams per kilogram (mg/kg) of ADCETRIS every three weeks for up to a maximum of eight doses. Patients who achieve partial remission or stable disease are eligible to receive an additional eight doses. Key findings, which were presented by Dr. Madeleine Duvic from The University of Texas MD Anderson Cancer Center, include:
Eleven of 17 evaluable patients (65 percent) achieved an objective response, including seven complete remissions (CRs) and four partial remissions (PRs). Six patients had stable disease. These investigator-assessed responses were observed in all three subtypes of CTCL.
The most common adverse events were Grade 1, including diarrhea, chest tightness, alopecia, nausea, elevated liver enzymes and peripheral neuropathy. ADCETRIS treatment was held in two patients with Grade 2 peripheral sensory neuropathy and in one patient with Grade 4 neutropenia and Grade 3 leukopenia. One patient died of sepsis after one dose of ADCETRIS.
Variable CD30 expression was observed in baseline lesions.
The clinical trial is ongoing with planned enrollment of 29 patients.
PTCL Case Studies
Data were also presented from case studies of two patients with relapsed CD30-positive PTCL-NOS who were enrolled in phase I trials of ADCETRIS. PTCL-NOS is associated with a poor prognosis and there is no well-established standard of care. Both patients were heavily pretreated, including prior autologous stem cell transplant. The first patient achieved a PR with progression-free survival of eight months and overall survival of 22 months. Adverse events considered related to ADCETRIS were Grade 2 sensory neuropathy in the fingertips and Grade 3 fatigue. The second patient achieved a CR which is still ongoing with a duration of more than 19 months. The patient had Grade 3 anemia and other Grade 1 adverse events, none of which were considered by the investigator to be related to ADCETRIS.
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: The Takeda Oncology Company 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 CTCL or PTCL-NOS.
ADCETRIS is not approved for use outside the United States. The marketing authorization application for ADCETRIS in relapsed or refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research & Development Centre (Europe), was accepted by the European Medicines Agency for review in June 2011.
Seattle Genetics and Millennium: The Takeda Oncology Company are planning a phase III clinical trial of ADCETRIS in CD30-positive CTCL patients to begin by mid-2012.
About CTCL
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. Cutaneous lymphomas are a category of non-Hodgkin lymphomas that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma that typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement is variable and may be accompanied by tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.
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.
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.
SOURCE: Seattle Genetics
Post Views: 68
