ZURICH, May 23, 2012 /PRNewswire/ --
− Data Show 86% of Patients Achieved an Objective Response Rate, with 57% of Patients Achieving Complete Remission −
Results from a pivotal phase II trial of brentuximab vedotin, published in the Journal of Clinical Oncology, showed that 86% of patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL), achieved the primary endpoint of objective response rate (ORR; complete remission (CR) and partial remission (PR) combined). Brentuximab vedotin is an antibody-drug conjugate directed at CD30 cell surface antigens, a defining marker of sALCL.
The pivotal phase II trial evaluated the efficacy and safety of single-agent brentuximab vedotin in 58 patients with relapsed or refractory sALCL. Key data, included:
- 86% of patients achieved an ORR, with a median duration of response of 12.6 months [95% CI (5.7, not estimable, or NE)].
- 57% of patients achieved a CR, with a median duration of response of 13.2 months [95% (10.8, NE)].
- The most common (≥20%) treatment-related adverse events of any grade were peripheral sensory neuropathy (41%), nausea (40%), fatigue (38%), pyrexia (34%), diarrhoea (29%), rash (24%), constipation (22%) and neutropenia (21%).
- Adverse events of Grade 3 or higher were experienced by 60% of patients. Among events of Grade 3 or higher severity that occurred in the study, the most common were neutropenia (21%), thrombocytopenia (14%), peripheral sensory neuropathy (12%), and anaemia (7%).
"The types of patients involved in this clinical trial are historically difficult to treat, highlighting an evident unmet need in this patient group. The results seen with these sALCL patients are relatively uncommon, particularly with a single-agent therapy that has a generally manageable side effect profile," said Professor Tim Illidge, Professor of Targeted Therapy and Oncology, University of Manchester, The Christie NHS Foundation Trust, and a UK trialist.
The primary endpoint of the trial was ORR as assessed by independent central review using the stringent Cheson 2007 criteria. Secondary endpoints included CR rate, duration of response, progression-free survival, overall survival and the incidence and severity of adverse events per independent central review.
Patients received 1.8 milligrams per kilogram of brentuximab vedotin every three weeks until disease progression, or up to a maximum of 16 total doses. The median age of patients was 52 years. Enrolled patients had received a median of two prior chemotherapy regimens and 62% of patients were primary refractory. Seventy-two percent of patients were anaplastic lymphoma kinase (ALK) negative, which is thought to be a poor prognosis factor. Twenty-two percent of patients had not responded to any prior treatment, and 26% had failed prior autologous stem cell transplant (ASCT).
Brentuximab vedotin does not currently have a licence in the European Union. The marketing authorisation application for brentuximab vedotin in relapsed or refractory HL and sALCL, filed by Takeda Global Research & Development Centre (Europe), was accepted by the European Medicines Agency for review in June 2011.
Date of preparation: May 2012
Job code: EU/ADC-010063
Notes to Editors
About brentuximab vedotin
Brentuximab vedotin is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilising 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 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 HL after failure of 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 brentuximab vedotin are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with brentuximab vedotin.
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: HL and non-Hodgkin lymphoma (NHL). NHL 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 Organisation identifies 22 subtypes of mature T- and NK-cell neoplasms, including systemic ALCL which is an aggressive type of T-cell NHL that expresses CD30. Other mature T-cell lymphomas include Peripheral T-Cell Lymphoma (PTCL), angioimmunoblastic T-cell lymphoma and adult T-cell lymphoma.
Word Definition Relapsed Return of disease after initial improvement following treatment Refractory Disease does not respond to treatment Partial remission A decrease in size of a tumour, or disease throughout the body, in response to treatment Complete remission Disappearance of all signs of cancer in response to treatment Overall objective Overall measurable response i.e. partial response remission and complete remission combined Autologous Stem Cell Removal, storage, and transplantation of Transplant (ASCT) the patient's own stem cells
About Takeda Pharmaceuticals International GmbH
Takeda Pharmaceuticals International GmbH, headquartered in Zurich, is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. As the largest pharmaceutical company in Japan and a leader in the global industry, Takeda's mission is to strive toward better health for patients worldwide through leading innovation in medicine. It has a commercial presence covering more than 70 countries, with particular strength in Asia, North America, Europe and fast-growing emerging markets including Latin America, Russia-CIS and China. Takeda is ranked 12th by global Rx sales, 14th in the BRIC countries and 18th in Europe. Takeda's commercial presence mainly covers the therapeutic areas of metabolic diseases, gastroenterology, oncology, cardiovascular health, CNS diseases, inflammatory and immune disorders, respiratory diseases and pain management.
Additional information about Takeda is available through its corporate website, http://www.takeda.com.
- B. Pro et al. Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma: Results of a Phase 2 study. JCO.2011.38.0402; published online on May 21, 2012. http://jco.ascopubs.org/content/early/2012/05/18/JCO.2011.38.0402.full.pdf
- Lymphoma Association. Information and support. What is Lymphoma? Available at: http://www.lymphomas.org.uk (Last accessed: 08.02.2012.)
- British Committee for Standards in Haematology. Guidelines for the Management of Mature T-cell and NK-cell Neoplasms. Available at: http://www.bcshguidelines.com/documents/T-cell_guideline_final_bcsh.pdf. (Last accessed: 28.02.2012)
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