Millennium reports results from two VELCADE based combination studies against multiple myeloma

Jun 8 2011

Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited (TSE:4502) today reported results from two studies of VELCADE^® (bortezomib) for Injection based combinations in patients with relapsed or refractory multiple myeloma (MM). The first study investigated the safety and efficacy of VELCADE in combination with LY2127399, a human monoclonal antibody. The second study assessed the safety and efficacy of VELCADE in combination with panobinostat. These data were presented at the annual meeting of the American Society of Clinical Oncology, held June 3 through 7 in Chicago, Illinois.

"These two studies provide encouraging evidence of VELCADE's utility as a backbone for novel combinations," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "We are especially pleased to see activity from VELCADE based combinations in these heavily pre-treated patient populations, including those who were refractory to VELCADE."

Phase I study of LY2127399, a human anti-BAFF antibody, and bortezomib in patients with previously treated multiple myeloma

The primary objective of this Phase I study in 20 patients was to identify an efficacious dose of LY2127399 with VELCADE. Sixty-five percent of patients had received prior treatment with VELCADE. The results, which were presented by Noopur Raje, M.D., Massachusetts General Hospital, showed:

• The median number of cycles completed was 5, and no dose-limiting toxicities (DLTs) were observed
• The 100 mg dose of LY was selected for further study with VELCADE
• The most common grade 3/4 adverse events were thrombocytopenia (15 percent), neutropenia (10 percent), diarrhea (10 percent) and neuropathy (10 percent)
• Overall response rate (ORR) was 55 percent
• Ten percent of patients achieved a complete response (CR), 15 percent of patients achieved a very good partial response (VGPR) and 30 percent of patients achieved a partial response (PR)
• The median duration of response was 9.7 months

VELCADE was given at 1.3 mg/m2 IV on days 1, 4, 8, and 11 q21d and LY at 1, 10, 30, 100, or 300 mg IV (30 min) on day 1 in Cycles 1 - 3, and every other cycle thereafter. Corticosteroids were not allowed. Response was assessed per IMWG criteria and adverse events per CTCAE v3.0. Pharmacokinetics (PK) were assessed, and pharmacodynamic studies included B-cell immunophenotyping and serum markers of bone turnover. (Abstract #8012)

A phase Ib study of oral panobinostat and IV bortezomib in relapsed and refractory multiple myeloma

This Phase Ib study of 62 relapsed or relapsed and refractory multiple myeloma patients assessed the safety and efficacy of VELCADE in combination with panobinostat. Forty-five percent of patients had received prior treatment with VELCADE, and 31 percent were refractory to VELCADE. The results, which were presented by Jesus San Miguel, M.D., Ph.D., Hospital Universitario de Salamanca, showed:

• Maximum tolerated dose was established as 20 mg of panobinostat plus 1.3 mg/m² of VELCADE
• The most common grade 3/4 adverse events were thrombocytopenia (79 percent), neutropenia (55 percent) and leukopenia (30 percent)
• Across all dosing cohorts, ORR was 55 percent
• Among VELCADE-refractory patients, ORR was 42 percent

This phase Ib study of relapsed or relapsed and refractory multiple myeloma completed enrollment>2 VELCADE. In the expansion phase, 15 patients received the MTD of panobinostat and VELCADE, with a modified panobinostat schedule (2 weeks on, 1 week off) and dexamethasone introduced for all patients at C2. This is identical to the dose and schedule in the ongoing phase II and III PANORAMA trials. (Abstract #8075)

Source: Millennium: The Takeda Oncology Company