Seattle Genetics, Inc., a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer, has announced that interim results from an investigator-sponsored phase II clinical trial of ADCETRIS (brentuximab vedotin) in patients with relapsed cutaneous T-cell lymphoma (CTCL) were presented at the Society for Investigative Dermatology annual meeting being held May 9-12, 2012 in Raleigh, NC. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS has not been approved for use in CTCL.

The trial enrolled CTCL patients with mycosis fungoides (MF) or Sezary syndrome. At the time of data analysis, 17 patients had been enrolled, including 16 with MF and one with Sezary syndrome. Patients had received a median of six prior therapies, including a median of four prior systemic therapies. The primary endpoint of the trial is clinical response rate. Secondary endpoints include correlation of clinical response with CD30 expression levels, duration of response, progression-free survival and safety.

The study is led by principal investigator Dr. Youn H. Kim, Professor, Department of Dermatology, and Director, Multidisciplinary Cutaneous Lymphoma Program at Stanford University School of Medicine in Stanford, CA. Key findings include:  Twelve of 16 evaluable patients (75 per cent) achieved a partial remission. Three patients had stable disease and one patient had progressive disease. One patient was not yet evaluable for response;  Median CD30 expression on lymphoid cells in biopsies of skin lesions was 15 per cent. Clinical activity was not dependent on CD30 expression levels; Sixty-eight percent of patients maintained response at week 25. Median duration of response had not yet been reached; Adverse events were mostly Grade 1 or 2, with the most common related events being peripheral neuropathy (76 per cent), fatigue (65 per cent), decreased appetite (30 per cent) and generalized skin eruption (30 per cent). The most common event of Grade 3 or higher was generalized skin eruption (18 per cent). One patient experienced Grade 4 peripheral neuropathy. There was one patient death due to respiratory failure presumably secondary to pneumonia.

This is the second data set reported with ADCETRIS in CTCL patients. At the T-Cell Lymphoma Forum in January 2012, interim data were presented from a phase II investigator-sponsored trial in CD30-positive CTCL patients, including lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma (pcALCL) or MF. In the trial, which is being conducted by Dr. Madeleine Duvic at The University of Texas MD Anderson Cancer Center, 11 of 17 evaluable patients (65 percent) achieved an objective response, including seven complete remissions (CRs) and four partial remissions (PRs). The most common adverse events were Grade 1, including diarrhoeaa, chest tightness, alopecia, nausea, elevated liver enzymes and peripheral neuropathy.

Seattle Genetics and Millennium: The Takeda Oncology Company recently initiated a randomized phase III clinical trial of ADCETRIS for relapsed CD30-positive CTCL patients. The trial will assess ADCETRIS versus investigator’s choice of methotrexate or bexarotene in patients with CD30-positive CTCL, including those with pcALCL or MF. The primary endpoint of the study is overall response rate lasting at least 4 months. Approximately 124 patients will be enrolled in the pivotal trial. The phase III trial is being conducted under a Special Protocol Assessment agreement from the US Food and Drug Administration (FDA). The study also received European Medicines Agency scientific advice.

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 and 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 tumour formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs. According to published literature, up to 50 percent of CTCL patients’ lesions express CD30.

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 tumour cells.

ADCETRIS (brentuximab vedotin) received accelerated approval from the US Food and Drug Administration 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 systemic anaplastic large cell lymphoma (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 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 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.