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

Swaminathan P. Iyer, Joseph Taddeus Beck, A. Keith Stewart, Jatin Shah, Kevin R. Kelly, Randi Isaacs, Sanela Bilic, Suman Sen, Nikhil C. Munshi

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

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 3-40 mg/kg. No DLTs 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. 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.

Original languageEnglish (US)
Pages (from-to)366-375
Number of pages10
JournalBritish journal of haematology
Volume167
Issue number3
DOIs
StatePublished - Nov 1 2014

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Keywords

  • BHQ880
  • Multiple myeloma
  • Phase I
  • Skeletal-related event

ASJC Scopus subject areas

  • Hematology

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