Data from two phase Ib clinical trials of dacetuzumab for DLBCL reported

Dec 8 2009

Seattle Genetics, Inc. (Nasdaq:SGEN) today reported data from two phase Ib clinical trials of dacetuzumab, one in combination with Rituxan® (rituximab) and Gemzar® (gemcitabine) for diffuse large B-cell lymphoma (DLBCL), and the other in combination with Revlimid® (lenalidomide) for multiple myeloma. In addition, data were reported describing a diagnostic gene signature that may identify lymphoma patients who are more likely to respond to dacetuzumab therapy. Dacetuzumab is a humanized antibody targeting CD40 that the company is developing under a worldwide collaboration agreement with Genentech, a wholly owned member of the Roche Group. The data were presented during the American Society of Hematology (ASH) 51^st Annual Meeting being held in New Orleans, Louisiana.

“Data from these two phase Ib trials demonstrate that dacetuzumab is well tolerated in combination with other therapies commonly used in the treatment of DLBCL and multiple myeloma,” said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. “The objective responses observed in these heavily pre-treated patients provide rationale to further assess the contribution of dacetuzumab to these combination therapies. With Genentech, we are continuing to evaluate next steps in these settings, and are also enrolling patients to two additional combination phase Ib trials for follicular lymphoma and multiple myeloma from which data are planned in 2010.”

DLBCL Phase Ib Trial

This single-arm trial enrolled 33 patients with relapsed or refractory DLBCL who received escalating doses of dacetuzumab ranging from 4 milligrams per kilogram (mg/kg) to 12 mg/kg in combination with Rituxan and Gemzar. Patients were heavily pre-treated, with a median of three prior systemic therapies, and the median age was 67 years. Ninety-seven percent had previously received a Rituxan-containing regimen.

The combination was generally well-tolerated and no maximum tolerated dose was determined. The majority of adverse events were Grade 1 or 2 in severity. The most common adverse events were nausea, fatigue and thrombocytopenia. Objective responses were achieved in 50 percent of patients (15 out of 30 patients with response assessments), including eight with complete responses and seven with partial responses. The median duration of response was 5.1 months. (Abstract # 586)

Multiple Myeloma Phase Ib Trial

This single-arm trial enrolled 36 patients with relapsed or refractory multiple myeloma who received escalating doses of dacetuzumab ranging from 4 mg/kg to 12 mg/kg in combination with Revlimid and weekly dexamethasone. Patients had a median age of 64.5 years and had received a median of four prior cancer-related therapies. Fifty percent of patients had received prior Revlimid.

The combination was generally well-tolerated and no maximum tolerated dose was identified. The majority of adverse events were Grade 1 or 2 in severity. The most common adverse events were fatigue, neutropenia, and thrombocytopenia. Objective responses were achieved in 44 percent of patients (16 out of 36 patients), including two complete responses and 14 partial responses. The objective response rate was 61 percent for patients who were Revlimid-naïve and 28 percent for those who had previously received Revlimid. (Abstract # 2870)

Dacetuzumab Gene Signature

Data were presented describing a diagnostic gene signature that may identify lymphoma patients who are more likely to respond to dacetuzumab therapy. In a retrospective analysis of patient samples from single-agent phase I and phase II trials, the data demonstrate that the gene signature correlated with sensitivity to treatment with dacetuzumab with an overall accuracy of 80 percent. In addition, patients predicted to respond to dacetuzumab therapy exhibited a longer progression-free survival than patients who did not express the gene signature. (Abstract # 2721)