A single-arm, open-label, phase 2 clinical trial evaluating disease response following treatment with BI-505, a human anti-intercellular adhesion molecule-1 monoclonal antibody, in patients with smoldering multiple myeloma

Stina Wichert, Gunnar Juliusson, Åsa Johansson, Elisabeth Sonesson, Ingrid Teige, Anna Teige Wickenberg, Björn Frendeus, Magnus Korsgren, Markus Hansson, Stina Wichert, Gunnar Juliusson, Åsa Johansson, Elisabeth Sonesson, Ingrid Teige, Anna Teige Wickenberg, Björn Frendeus, Magnus Korsgren, Markus Hansson

Abstract

Background: Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects. BI-505 was well tolerated in an earlier phase 1 trial.

Methods and findings: In this phase 2 trial the effects of BI-505 in patients with SMM were studied. Four patients were enrolled and three of them completed the first cycle of treatment defined as 5 doses of BI-505, a total of 43 mg/kg BW, over a 7-week period. In the three evaluable patients, BI-505 showed a benign safety profile. None of the patients achieved a response as defined per protocol. EudraCT number: 2012-004884-29.

Conclusions: The study was conducted to assess the efficacy, safety and pharmacodynamics of BI-505 in patients with SMM. BI-505 showed no clinically relevant efficacy on disease activity in these patients with SMM, even if well tolerated.

Trial registration: ClinicalTrials.gov Identifier: NCT01838369.

Conflict of interest statement

We have the following interests: ES, IT, ATW, BF, MK are, or were, full-time employees of BioInvent International AB at the time of this study. IT, ATW and BF are currently employed and own stock (>50,000) in the company. BF and MH are inventors on patents relating to BI-505 and anti-ICAM antibody therapy. These declarations do not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Fig 1. CONSORT flowchart for A single-arm,…
Fig 1. CONSORT flowchart for A single-arm, open-label, phase 2 clinical trial with BI-505, a human anti-intercellular adhesion molecule-1 monoclonal antibody, in patients with smoldering multiple myeloma.
Fig 2. Reduced proportions of monocytes, NK…
Fig 2. Reduced proportions of monocytes, NK and NKT cells after the first dose of BI-505.
Percentage of monocytes, NK and NKT cells in blood samples collected before and immediately after completion of the first BI-505 infusion in patients No 2 and No 3, as analyzed by flow cytometry.

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