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

Abstract

BackgroundSmoldering 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 findingsIn 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.ConclusionsThe 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 registrationClinicalTrials.gov Identifier: NCT01838369.

ICAM-1-LFA-1 Dependent CD8+ T-Lymphocyte Aggregation in Tumor Tissue Prevents Recirculation to Draining Lymph Nodes

“…The first one entailed a Phase I dose-escalation study in patients suffering from advance relapsed/refractory multiple myeloma ( 49 ). The second assay consisted in an open arm-phase 2 clinical trial enrolling four patients diagnosed with smoldering multiple myeloma and showed no relevant clinical activity although treatment was well tolerated ( 50 ). Interestingly, a Phase I/II study of BI-505 in conjunction with autologous stem cell transplant in multiple myeloma (NCT02756728) was terminated due to and adverse cardiopulmonary event in the clinical study (as reported in the informative press note released by BioInvent in November 2016).…”

Urothelial bladder cancer may suppress perforin expression in CD8+ T cells by an ICAM-1/TGFβ2 mediated pathway

“…As a novel synergistic tumor immune escape was exerted by ICAM-1 and TGFβ2 signal, it opens a new potential in translational application. Interestingly, some clinical trials have been initiated to target ICAM-1 and TGFβ2 individually as the possibilities for future cancer immunotherapies [ 48 , 49 ]. This can further lead into combinations of immunotherapy as new strategies against cancer.…”

A novel Fc-engineered human ICAM-1/CD54 antibody with potent anti-myeloma activity developed by cellular panning of phage display libraries

“…Enlimomab (BIRR1/R6.5), another anti-human ICAM-1 antibody, was also tested in clinical trials to treat rheumatoid arthritis, prevent acute rejection of renal transplants and in acute stroke patients, and showed some clinical improvements for arthritis as well as stroke patients and importantly good tolerability [ 59 , 60 ]. The first human anti-ICAM-1 IgG1 mAb BI-505 was recently evaluated in clinical trials for patients with relapsed/refractory MM and smoldering myeloma [ 61 , 62 ]. Even though future clinical development was stopped, BI-505 was mostly well tolerated.…”