Seattle Genetics (SGEN) Updates on ADCETRIS in Relapsed HL
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Seattle Genetics, Inc. (Nasdaq: SGEN) summarized ADCETRIS (brentuximab vedotin) data in relapsed Hodgkin lymphoma (HL) and other CD30-positive malignancies from multiple presentations at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. Highlights include compelling survival data from long-term follow up in a pivotal clinical trial of ADCETRIS in relapsed or refractory HL and a retrospective comparison of overall survival among patients treated with ADCETRIS to those not treated with ADCETRIS following an autologous stem cell transplant (ASCT). In addition, data describe the activity and tolerability of ADCETRIS in the salvage HL setting from an investigator-sponsored trial and in relapsed patients age 60 or over with CD30-positive malignancies, including HL. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL.
"There are more than a dozen data presentations at ASH evaluating the use of ADCETRIS in CD30-positive malignancies and we are very encouraged by both the broad application across multiple hematologic disease areas as well as the encouraging activity associated with ADCETRIS,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “The extensive investigator and corporate data presentations at ASH clearly demonstrate the important role ADCETRIS plays in the treatment of relapsed HL and systemic anaplastic large cell lymphoma and the promise of the role it potentially will play in additional future indications.”
Long-term Survival Analysis of an Ongoing Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #3689)
A pivotal, single-arm trial was conducted in 102 relapsed or refractory HL patients after ASCT to assess efficacy and safety of single-agent ADCETRIS. In addition, the trial was designed to determine duration of response, progression-free survival and overall survival. Enrolled patients had received a median of more than three prior chemotherapy regimens.
Data highlights from the long-term survival analysis in the pivotal trial were:
* After a median observation time of approximately 2.5 years from first dose of ADCETRIS, 59 percent of patients (60 of 102 patients) were alive and the median overall survival had not yet been reached.
* The estimated two year survival rate was 65 percent, including 91 percent for patients who achieved a complete remission.
* Improved overall survival and progression-free survival correlated with PET (positron emission tomography) evaluation at Cycle four.
* There was no significant difference in prolonged overall survival in patients whose disease progressed less than or more than one year following ASCT. The only pretreatment factor that was associated with a higher two year survival rate was a baseline ECOG score of 0.
* The most common adverse events of any grade were peripheral sensory neuropathy (47 percent), fatigue (46 percent), nausea (42 percent), upper respiratory tract infection (37 percent) and diarrhea (36 percent).
* Among the most common adverse events of any grade, the most common Grade 3 or 4 adverse events were neutropenia (14 percent Grade 3, 6 percent Grade 4) and peripheral sensory neuropathy (9 percent Grade 3). Other Grade 3 or 4 adverse events occurring in at least five percent of patients were thrombocytopenia (8 percent) and anemia (6 percent).
Overall Survival Benefit for Patients with Relapsed Hodgkin Lymphoma Treated with Brentuximab Vedotin After Autologous Stem Cell Transplant (Abstract #3701)
An independent retrospective comparison conducted by MD Anderson Cancer Center evaluated overall survival in 102 relapsed HL patients treated with ADCETRIS in a pivotal clinical trial compared to data from 756 relapsed HL patients treated at six international centers (Horning et al., 2008). The authors compared median overall survival, starting at the time of receiving an ASCT, among ADCETRIS treated patients to patients not treated with ADCETRIS. Key findings, which were highlighted in a presentation by Dr. Meghan Karuturi from MD Anderson Cancer Center, included:
* Median overall survival following the date of ASCT in ADCETRIS treated patients was 91.49 months compared to 27.99 months in those not treated with ADCETRIS (p<0.0001).
* In an analysis evaluating predictors of patients who achieved a durable complete remission with ADCETRIS, only the stage of disease at initial diagnosis had a significant effect on overall survival.
Brentuximab Vedotin as a First Line Salvage Therapy in Relapsed/Refractory HL (Abstract #3699)
An investigator-sponsored trial was conducted to evaluate ADCETRIS as a salvage therapy for HL. Fourteen patients were evaluated for response and safety and all had relapsed or refractory HL after initial therapy with the chemotherapy regimens ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) or BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, Oncovin, procarbazine hydrochloride, prednisone) or a combination of chemotherapy with or without consolidative radiation treatment. Patients were treated with ADCETRIS every three weeks for a maximum of four cycles. Data were presented by Dr. Robert Chen from City of Hope National Medical Center in Duarte, CA.
Data highlights were:
* Of the 14 patients evaluable at the time of this analysis, the objective response rate was 85.7 percent (12 of 14 patients), including 50 percent (seven of 14 patients) with a complete remission and 35.7 percent (five of 14 patients) with a partial remission. Two patients achieved stable disease after four cycles of therapy. No patients developed progressive disease while on treatment.
* At the time of data analysis, a total of seven of 14 patients had undergone stem cell mobilization after the fourth dose of ADCETRIS and 100 percent of these patients achieved complete remission after stem cell transplantation. The other seven patients were still undergoing stem cell mobilization or had not completed ADCETRIS treatment.
* The most common adverse events of Grade 1 or 2 were peripheral sensory neuropathy (42.9 percent), rash acneiform (35.7 percent), AST elevation (28.6 percent) and fatigue (28.6 percent).
* Grade 3 adverse events were rash acneiform (7.1 percent) and urinary tract infection (7.1 percent). There were no Grade 4 adverse events.
ADCETRIS is not approved for salvage HL patients who are deemed eligible for ASCT. There are multiple ongoing investigator-sponsored trials being conducted evaluating ADCETRIS as a salvage HL therapy, and a phase I/II clinical trial evaluating ADCETRIS with bendamustine in this setting will be initiated by the end of 2012.
Retrospective Analysis of the Safety and Efficacy of Brentuximab Vedotin in Patients Aged 60 Years or Older with Relapsed or Refractory CD30+ Hematologic Malignancies (Abstract #3687)
A retrospective analysis was conducted in patients at least 60 years or older with CD30-positive hematologic malignancies who had received at least one dose of ADCETRIS in one or more of seven clinical trials. The analysis assessed the efficacy and safety of single-agent ADCETRIS among 22 systemic anaplastic large cell lymphoma (sALCL) patients, 16 HL patients and two patients with other CD30-positive malignancies.
Data highlights from the retrospective analysis of ADCETRIS treated patients age 60 and older were:
* Of the 40 patients evaluated, 33 patients (83 percent) had an objective response, including 18 (45 percent) complete remissions and 15 (38 percent) partial remissions.
* Of the 22 patients with sALCL and two patients with other CD30-positive malignancy, all 24 patients (100 percent) achieved an objective response. Of the 16 patients with HL, nine patients (56 percent) achieved an objective response.
* The incidence of adverse events was generally similar in older and younger patients, with peripheral sensory neuropathy, fatigue and anemia appearing to be more common among patients age 60 or older. Adverse events were manageable with dose modifications or delays.
* The most common adverse events of any grade with an incidence greater than 25 percent were peripheral sensory neuropathy (60 percent), fatigue (58 percent), nausea (38 percent), anemia (30 percent), fever (28 percent), diarrhea (25 percent) and neutropenia (25 percent).
* The most common Grade 3 or 4 adverse events were neutropenia (25 percent), anemia (20 percent), peripheral sensory neuropathy (15 percent), fatigue (10 percent) and thrombocytopenia (10 percent).
"There are more than a dozen data presentations at ASH evaluating the use of ADCETRIS in CD30-positive malignancies and we are very encouraged by both the broad application across multiple hematologic disease areas as well as the encouraging activity associated with ADCETRIS,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “The extensive investigator and corporate data presentations at ASH clearly demonstrate the important role ADCETRIS plays in the treatment of relapsed HL and systemic anaplastic large cell lymphoma and the promise of the role it potentially will play in additional future indications.”
Long-term Survival Analysis of an Ongoing Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #3689)
A pivotal, single-arm trial was conducted in 102 relapsed or refractory HL patients after ASCT to assess efficacy and safety of single-agent ADCETRIS. In addition, the trial was designed to determine duration of response, progression-free survival and overall survival. Enrolled patients had received a median of more than three prior chemotherapy regimens.
Data highlights from the long-term survival analysis in the pivotal trial were:
* After a median observation time of approximately 2.5 years from first dose of ADCETRIS, 59 percent of patients (60 of 102 patients) were alive and the median overall survival had not yet been reached.
* The estimated two year survival rate was 65 percent, including 91 percent for patients who achieved a complete remission.
* Improved overall survival and progression-free survival correlated with PET (positron emission tomography) evaluation at Cycle four.
* There was no significant difference in prolonged overall survival in patients whose disease progressed less than or more than one year following ASCT. The only pretreatment factor that was associated with a higher two year survival rate was a baseline ECOG score of 0.
* The most common adverse events of any grade were peripheral sensory neuropathy (47 percent), fatigue (46 percent), nausea (42 percent), upper respiratory tract infection (37 percent) and diarrhea (36 percent).
* Among the most common adverse events of any grade, the most common Grade 3 or 4 adverse events were neutropenia (14 percent Grade 3, 6 percent Grade 4) and peripheral sensory neuropathy (9 percent Grade 3). Other Grade 3 or 4 adverse events occurring in at least five percent of patients were thrombocytopenia (8 percent) and anemia (6 percent).
Overall Survival Benefit for Patients with Relapsed Hodgkin Lymphoma Treated with Brentuximab Vedotin After Autologous Stem Cell Transplant (Abstract #3701)
An independent retrospective comparison conducted by MD Anderson Cancer Center evaluated overall survival in 102 relapsed HL patients treated with ADCETRIS in a pivotal clinical trial compared to data from 756 relapsed HL patients treated at six international centers (Horning et al., 2008). The authors compared median overall survival, starting at the time of receiving an ASCT, among ADCETRIS treated patients to patients not treated with ADCETRIS. Key findings, which were highlighted in a presentation by Dr. Meghan Karuturi from MD Anderson Cancer Center, included:
* Median overall survival following the date of ASCT in ADCETRIS treated patients was 91.49 months compared to 27.99 months in those not treated with ADCETRIS (p<0.0001).
* In an analysis evaluating predictors of patients who achieved a durable complete remission with ADCETRIS, only the stage of disease at initial diagnosis had a significant effect on overall survival.
Brentuximab Vedotin as a First Line Salvage Therapy in Relapsed/Refractory HL (Abstract #3699)
An investigator-sponsored trial was conducted to evaluate ADCETRIS as a salvage therapy for HL. Fourteen patients were evaluated for response and safety and all had relapsed or refractory HL after initial therapy with the chemotherapy regimens ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) or BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, Oncovin, procarbazine hydrochloride, prednisone) or a combination of chemotherapy with or without consolidative radiation treatment. Patients were treated with ADCETRIS every three weeks for a maximum of four cycles. Data were presented by Dr. Robert Chen from City of Hope National Medical Center in Duarte, CA.
Data highlights were:
* Of the 14 patients evaluable at the time of this analysis, the objective response rate was 85.7 percent (12 of 14 patients), including 50 percent (seven of 14 patients) with a complete remission and 35.7 percent (five of 14 patients) with a partial remission. Two patients achieved stable disease after four cycles of therapy. No patients developed progressive disease while on treatment.
* At the time of data analysis, a total of seven of 14 patients had undergone stem cell mobilization after the fourth dose of ADCETRIS and 100 percent of these patients achieved complete remission after stem cell transplantation. The other seven patients were still undergoing stem cell mobilization or had not completed ADCETRIS treatment.
* The most common adverse events of Grade 1 or 2 were peripheral sensory neuropathy (42.9 percent), rash acneiform (35.7 percent), AST elevation (28.6 percent) and fatigue (28.6 percent).
* Grade 3 adverse events were rash acneiform (7.1 percent) and urinary tract infection (7.1 percent). There were no Grade 4 adverse events.
ADCETRIS is not approved for salvage HL patients who are deemed eligible for ASCT. There are multiple ongoing investigator-sponsored trials being conducted evaluating ADCETRIS as a salvage HL therapy, and a phase I/II clinical trial evaluating ADCETRIS with bendamustine in this setting will be initiated by the end of 2012.
Retrospective Analysis of the Safety and Efficacy of Brentuximab Vedotin in Patients Aged 60 Years or Older with Relapsed or Refractory CD30+ Hematologic Malignancies (Abstract #3687)
A retrospective analysis was conducted in patients at least 60 years or older with CD30-positive hematologic malignancies who had received at least one dose of ADCETRIS in one or more of seven clinical trials. The analysis assessed the efficacy and safety of single-agent ADCETRIS among 22 systemic anaplastic large cell lymphoma (sALCL) patients, 16 HL patients and two patients with other CD30-positive malignancies.
Data highlights from the retrospective analysis of ADCETRIS treated patients age 60 and older were:
* Of the 40 patients evaluated, 33 patients (83 percent) had an objective response, including 18 (45 percent) complete remissions and 15 (38 percent) partial remissions.
* Of the 22 patients with sALCL and two patients with other CD30-positive malignancy, all 24 patients (100 percent) achieved an objective response. Of the 16 patients with HL, nine patients (56 percent) achieved an objective response.
* The incidence of adverse events was generally similar in older and younger patients, with peripheral sensory neuropathy, fatigue and anemia appearing to be more common among patients age 60 or older. Adverse events were manageable with dose modifications or delays.
* The most common adverse events of any grade with an incidence greater than 25 percent were peripheral sensory neuropathy (60 percent), fatigue (58 percent), nausea (38 percent), anemia (30 percent), fever (28 percent), diarrhea (25 percent) and neutropenia (25 percent).
* The most common Grade 3 or 4 adverse events were neutropenia (25 percent), anemia (20 percent), peripheral sensory neuropathy (15 percent), fatigue (10 percent) and thrombocytopenia (10 percent).
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