A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events

作者：Iyer Swaminathan P^*; Beck Joseph Taddeus; Stewart A Keith; Shah Jatin; Kelly Kevin R; Isaacs Randi; Bilic Sanela; Sen Suman; Munshi Nikhil C

来源：British Journal of Haematology, 2014, 167(3): 366-375.

DOI：10.1111/bjh.13056

• BHQ880
• multiple myeloma
• skeletal-related event
• Phase I

Dickkopf-1 (DKK1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. BHQ880, a human neutralizing IgG1 anti-DKK1 monoclonal antibody, is being investigated for its impact on multiple myeloma-related bone disease and as an agent with potential anti-myeloma activity. The primary objectives of this Phase IB study were to determine the maximum tolerated dose (MTD) of BHQ880 and to characterize the dose-limiting toxicity (DLT) of escalating doses in combination with anti-myeloma therapy and zoledronic acid. Twenty-eight patients were enrolled and received BHQ880 at doses of 3-40mg/kg. No DLTs were reported, therefore, the MTD was not determined. The recommended Phase II dose was declared as 10mg/kg, based mainly on saturation data. There was a general trend towards increased bone mineral density (BMD) observed over time; specific increases in spine BMD from Cycle 12 onwards irrespective of new skeletal-related events on study were observed, and increases in bone strength at the spine and hip were also demonstrated in some patients. BHQ880 in combination with zoledronic acid and anti-myeloma therapy was well tolerated and demonstrated potential clinical activity in patients with relapsed or refractory multiple myeloma.

• 出版日期2014-11