Updated data from a pivotal trial of single-agent brentuximab vedotin (adcetris™,Seattle Genetics) in patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) presented at the 53rd Annual Meeting American Society of Hematology being held December 10 to 13, 2011 in San Diego, CA, shows durable complete remissions and treatment associated with manageable toxicity.

Brentuximab vedotin is an antibody-drug conjugate (ADC) that targets a protein known as CD30 which is expressed in Hodgkin lymphoma cells as well as cells from other cancers, including anaplastic large cell lymphoma. The anti-CD30 monoclonal antibody is attached by a protease-cleavable linker to a microtubule disrupting chemotherapy agent called monomethyl auristatin E (MMAE). Once the drug enters CD30-positive cells, it releases the chemotherapy drug.

“This clinical trial demonstrates that durable complete remissions can be achieved with Adcetris in this aggressive type of T-cell lymphoma that expresses CD30,” said Ranjana H. Advani, Professor of Medicine/Oncology at Stanford University Medical Center. “These data reinforce the role of Adcetris in relapsed or refractory systemic ALCL patients, and its potential to provide an important therapeutic option for eligible patients.”

A Phase II Study Update
One pivotal trial was conducted in 58 relapsed or refractory sALCL patients. The primary endpoint was overall objective response rate per independent review. Key updated data, presented by Dr. Advani showed that 86% of patients achieved an objective response with a median duration of 13.2 months. Fifty-nine percent of patients achieved a complete remission (CR). Median follow-up from first dose of brentuximab vedotin in all patients was 14.7 months. Median progression-free survival (PFS) in patients treated was 14.5 months compared to 5.9 months for the most recent prior therapy received by these patients. Median PFS of anaplastic lymphoma kinase (ALK)-positive patients was 14.6 months compared to 14.3 months in ALK-negative patients. Estimated overall survival rate of patients at one year was 70%.

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The single-arm trial assessed efficacy and safety of single-agent brentuximab vedotin in relapsed or refractory sALCL patients. Patients received 1.8 milligrams per kilogram of brentuximab vedotin every three weeks for up to 16 total cycles. The median age of patients in the pivotal trial was 52 years. Enrolled patients had received a median of two prior chemotherapy regimens.

Initial trial results
Durable complete remissions were achieved with brentuximab vedotin, and treatment was associated with manageable toxicity, in patients with relapsed or refractory sALCL. Approximately half of the responding patients (24 of 50) continued in remission at the time of this analysis.

Ongoing trials
Based on the results from this study, a trial evaluating the safety of brentuximab vedotin administered in sequence and in combination with multiagent chemotherapy was initiated and is currently ongoing in frontline sALCL.

Brentuximab vedotin is jointly developed by Seattle Genetics and Millennium: The TakedaOncology Company on a 50:50 basis. The drug was granted accelerated approval by the U.S. Food and Drug Administration in August 2011 for the treatment of patients with Hodgkin lymphoma (HL) 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 the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with Brentuximab vedotin.

Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.

Program: Oral and Poster Abstracts
Type: Oral
Abstract: 443 Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma: A Phase 2 Study Update
Session: 624. Lymphoma – Therapy with Biologic Agents, excluding Pre-Clinical Models: Mantle Cell and T Cell Lymphoma – Targeted Antibody and Small Molecule Approaches
When: Monday, December 12, 2011: 11:30 AM
Where: Ballroom 20A (San Diego Convention Center)

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