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A Phase IB multicentre dose‐determination study of BHQ 880 in combination with anti‐myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal‐related events
Author(s) -
Iyer Swaminathan P.,
Beck Joseph Taddeus,
Stewart A. Keith,
Shah Jatin,
Kelly Kevin R.,
Isaacs Randi,
Bilic Sanela,
Sen Suman,
Munshi Nikhil C.
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13056
Subject(s) - zoledronic acid , multiple myeloma , medicine , bone disease , combination therapy , phases of clinical research , refractory (planetary science) , oncology , toxicity , gastroenterology , pharmacology , osteoporosis , biology , astrobiology
Summary Dickkopf‐1 ( DKK 1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. BHQ 880, a human neutralizing IgG1 anti‐ DKK 1 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 BHQ 880 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 BHQ 880 at doses of 3–40 mg/kg. No DLT s were reported, therefore, the MTD was not determined. The recommended Phase II dose was declared as 10 mg/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. BHQ 880 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.