Pivotal PINNACLE trial results of VELCADE in patients with relapsed/refractory MCL released

Millennium: The Takeda Oncology Company today reported new correlative science data from the pivotal PINNACLE trial of VELCADE^® (bortezomib) in patients with relapsed/refractory mantle cell lymphoma (MCL). The data, derived from an analysis of archived tumor samples, tested pre-specified biomarkers for their association with time to progression and response to treatment with VELCADE in patients with relapsed MCL. The results add to the body of data supporting the potential usefulness of biomarkers in predicting outcome of MCL and predicting responsiveness to single agent VELCADE. The study is published in the July issue of Leukemia & Lymphoma.

“This analysis of the PINNACLE study opens the door for additional research into targeted approaches to VELCADE treatment.”

"Since its foundation Millennium has tried to find ways to better personalize therapy, and this trial is one example of our continued commitment to helping physicians and patients choose the most appropriate therapy for their disease," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "This analysis of the PINNACLE study opens the door for additional research into targeted approaches to VELCADE treatment."

"We look forward to the results of further studies, which will help us better understand the critical cellular pathways regulated by VELCADE, and ultimately accelerate clinical research in lymphoma by predicting which drugs could work best in individual patients in clinical trial settings," said lead author Andre Goy, M.D., M.S., Chief, Lymphoma, the John Theurer Cancer Center at Hackensack University Medical Center.

The biomarkers identified and their corresponding roles indicate:

• Elevated expression of NFKB p65 or low levels of PSMA5 were associated with longer time to progression and showed a trend toward better responses
• Elevated levels of p27 were associated with longer overall survival
• The poor outcomes in MCL predicted by elevated levels of Ki-67 were not overcome by VELCADE monotherapy

The PINNACLE trial was a Phase II, open-label, single-arm, multicenter study of 155 patients with relapsed/refractory MCL and was the basis of the 2006 approval of VELCADE for the treatment of patients with relapsed/refractory MCL who had received one prior therapy. The overall response rate in the trial was 31 percent, with a median duration of response of 9.3 months; the CR rate was 8 percent, with a median duration of response of 15.4 months.

The Goy analysis used archived tumor samples from 73 patients who participated in the PINNACLE trial. The biopsies were examined for biomarkers associated with poor prognosis in MCL or those regulated by the proteasome. The biomarker levels were then compared to the effect of VELCADE on patients, according to response rates including overall survival and time to progression.