Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma

Dan T. Vogl, Thomas G. Martin, Ravi Vij, Parameswaran Hari, Joseph R. Mikhael, David Siegel, Ka Lung Wu, Michel Delforge, Cristina Gasparetto

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41 Scopus citations

Abstract

Delanzomib (CEP-18770), a reversible P2 threonine boronic acid proteasome (β5/β1 subunits) inhibitor that showed promising anti-myeloma effects in preclinical studies, was investigated in a single-agent multicenter phase I/II study in patients with relapsed/refractory myeloma. Sixty-one patients (17 during dose escalation; 44 in the expansion cohort) received delanzomib on days 1, 8, and 15 in 28-d cycles; 47 received the maximum tolerated dose (MTD), 2.1 mg/m2. Dose-limiting toxicities (DLTs) at 2.4 mg/m2 were rash and thrombocytopenia. At the MTD, the most prominent adverse events were nausea, vomiting, anorexia, fatigue, and pyrexia; grade 3/4 thrombocytopenia and neutropenia occurred in 53 and 23% of patients, respectively. Peripheral neuropathy (21%) was limited to grades 1/2. At the MTD, 26 patients (55%) had stable disease and four (9%) had a partial response (PR). Median time to progression (TTP) was 2.5 months across the cohort. Based upon the efficacy results, development of delanzomib for myeloma was discontinued.

Original languageEnglish
Pages (from-to)1872-1879
Number of pages8
JournalLeukemia and Lymphoma
Volume58
Issue number8
DOIs
StatePublished - Aug 3 2017

Keywords

  • CEP-18770
  • Delanzomib
  • phase I/II study
  • proteasome inhibitor
  • relapsed/refractory multiple myeloma

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