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

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.

Keywords:

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

Acknowledgments

This research was sponsored by and conducted by Teva Branded Pharmaceutical Products R&D, Inc., Frazer, PA. Funding for editorial support was provided by Teva Branded Pharmaceutical Products R&D, Inc., to The Curry Rockefeller Group, LLC, Tarrytown, NY, USA.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online (http://dx.doi.org/10.1080/10428194.2016.1263842).