Seattle Genetics today announced updated results from a phase 2 clinical trial of brentuximab vedotin (Adcetris®) in diffuse large B-cell lymphoma (DLBCL) and other B-cell non-Hodgkin lymphomas. The data, which demonstrated an encouraging activity and tolerability profile in the relapsed and refractory setting, were presented in an oral presentation at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in New Orleans, Louisiana, December 7-10, 2013. Adcetrisis an antibody-drug conjugate (ADC) directed to CD30. Adcetris is currently not approved for the treatment of DLBCL or other B-cell lymphomas.
“In DLBCL, patients with relapsed or refractory disease have poor outcomes, and there is a significant need for better therapeutic approaches to treat this aggressive non-Hodgkin lymphoma subtype,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “We are encouraged by the interim phase 2 results which demonstrated that single-agent Adcetris induced a 42 percent objective response rate and manageable safety profile among advanced DLBCL patients, including a high percentage whose disease was refractory to their prior therapy. Based on these data, we have expanded our clinical program for Adcetris in DLBCL both as a single-agent and in combination with standard regimens for both relapsed and newly diagnosed patients.”
A Phase II Study of Brentuximab Vedotin in Patients with Relapsed or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results in Patients with DLBCL and Other B-cell Lymphomas (Abstract #848)
Interim data from an ongoing phase 2 clinical trial were reported from 50 patients with DLBCL and 18 patients with other B-cell lymphomas. Among the DLBCL patients, the median age was 63 years, 74 percent were refractory to frontline therapy and 82 percent were refractory to their most recent prior therapy. Patients were treated with single-agent ADCETRIS every three weeks. The trial was designed to assess the antitumor activity, duration of response and safety profile of ADCETRIS in these patients. Key findings presented by Dr. Nancy Bartlett from the Washington University, Siteman Cancer Center in St. Louis, MO, included:
- Of the 50 patients with DLBCL, 42 percent achieved an objective response, including 16 percent complete remissions and 26 percent partial remissions.
- At the time of data analysis, the median duration of response for DLBCL was 5.8 months. For DLBCL patients who achieved a complete remission, the median duration of response was 11.5 months.
- Objective responses were observed across a broad range of CD30 expression, from DLBCL patients with undetectable CD30 by standard immunohistochemistry testing to those with CD30 expression up to 90 percent.
- The most common treatment-emergent adverse events of any grade in patients with DLBCL and other B-cell lymphomas occurring in more than 25 percent of all patients enrolled were fatigue (49 percent), neutropenia (40 percent), nausea (38 percent), diarrhea (37 percent) and fever (29 percent).
- The most common Grade 3 treatment-emergent adverse events in patients with DLBCL and other B-cell lymphomas were neutropenia and anemia. The only Grade 4 treatment-emergent event was neutropenia. Serious adverse events considered related to treatment and occurring in more than one patient were pneumonia (three patients) and anemia, febrile neutropenia, neutropenia and thrombocytopenia (two patients each).
These encouraging findings support Seattle Genetics’ ongoing evaluation of Adcetris as a treatment for DLBCL. The phase 2 clinical trial presented at ASH has been expanded to include a treatment arm to assess the activity and tolerability of Adcetris in combination with Rituxan (rituximab) as well as an arm to evaluate single-agent Adcetris in patients with undetectable CD30 expression using standard immunohistochemistry methods. In addition, a phase 2 trial was recently initiated to evaluate Adcetris plus R-CHOP in newly diagnosed, high-risk DLBCL patients, regardless of CD30 expression level.