Trial Demonstrates High Response Rate In Lymphoma Patients

Pharmacyclics announced final data from a Phase 1/2 study showing a 46 percent complete response rate in patients with multiply recurrent non-Hodgkin's lymphoma (NHL) who were treated with motexafin gadolinium (MGd, Xcytrin) in combination with Yttrium-90 Ibritumomab Tiuxetan (Zevalin), an approved antibody-targeted radiation therapy. The data were presented during the 10th International Conference on Malignant Lymphoma being held this week in Lugano, Switzerland.

The Phase 1/2 study was conducted in 29 patients with advanced relapsed lymphomas, including 11 patients with aggressive lymphomas. Eighty-three percent of the patients were rituximab (Rituxan) refractory. Patients were treated with a standard dose of Zevalin administered with 2.5 to 5.0 mg/kg of MGd given for six days. Of 28 evaluable patients, 46 percent showed a complete response and 11 percent showed a partial response for an overall response rate of 57 percent. Rituximab refractory patients showed an overall response rate of 86 percent, with a 64 percent complete response rate and a median time to progression of 14 months. Adverse events seen were related to bone marrow suppression, an expected side effect of treatment with Zevalin.

"Motexafin gadolinium has been shown to have single agent activity in lymphoma and is synergistic with radiation therapy. This study shows a high rate of durable complete responses, especially in rituximab refractory patients," said Andrew M. Evens, D.O., M.S., Department of Hematology/Oncology, Northwestern University Feinberg School of Medicine, and lead author of the study.

Pharmacyclics has been developing MGd for use in combination with radiation therapy for treatment of brain metastases from lung cancer. A previous phase 3 trial showed that the addition of MGd to whole brain radiation therapy (WBRT) improved the median time to neurologic progression from 10.0 months to 15.4 months (P=0.12). At the 2007 American Society of Clinical Oncology Annual Meeting (ASCO), Pharmacyclics announced final results from a Phase 2 clinical trial in patients with brain metastases indicating that MGd improved the efficacy of targeted stereotactic radiosurgery.

"These results in lymphoma are consistent with motexafin gadolinium's known synergy with radiation, especially with targeted radiation therapy given over a short time as is the case with Zevalin, and with stereotactic radiation," said Richard A. Miller, M.D., president and chief executive officer of Pharmacyclics, and a co-author on the lymphoma study.

Zevalin is a radiolabeled antibody approved for treatment of patients with relapsed non-Hodgkin's lymphoma. Zevalin binds to tumor cells and emits radiation to the tumor site. Previously reported studies in the literature have shown that Zevalin alone produces a 15% complete response rate with median time to tumor progression of about seven months in rituximab refractory patients.