Background: Myeloma is an incurable disease that typically follows a relapsing course, with many patients (pts) requiring multiple lines of therapy. Outcomes in RRMM remain poor, particularly after failure of proteasome inhibitor (PI)- and/or immunomodulatory drug (IMiD)-based treatment. There remains a need for novel, targeted therapies for RRMM. BI 836909, a bi-specific T-cell engager (BiTE) that binds CD3ε on T-cells and BCMA on plasma cells, has demonstrated anti-myeloma activity in preclinical models (Hipp et al. ASH 2015; abs 2999). Here we report the design and objectives of the first in-human trial of BI 836909 – a multicenter, open-label, two-part, Phase 1, dose-escalation study evaluating intravenous (IV) and subcutaneous (SC) formulations of BI 836909 in RRMM. Methods: Adult pts with RRMM after ≥ 2 prior lines of therapy (including a PI and IMiD) and ECOG PS ≤ 2 are eligible. In part A, pts will receive escalating doses (modified 3+3 design) of BI 836909 as a continuous IV infusion for 4 weeks in 6-week cycles. Dose escalation will proceed based on clinical findings observed during the first 2–4 weeks of cycle 1. Pts will receive up to 5 cycles of treatment (up to 10 cycles for ongoing clinical benefit, at the investigator’s discretion) in the absence of disease progression, unacceptable toxicity, or other reasons necessitating withdrawal. Initiation of part B to assess SC BI 836909 will be based on clinical data from part A with the IV formulation. In part B, pts will receive escalating doses (3+3 design) of BI 836909 as a daily SC injection for 4 weeks in 6-week cycles, with stopping criteria as in part A. The primary objective of parts A and B is to determine the maximum tolerated dose of BI 836909 IV/SC for subsequent expansion cohorts. Secondary objectives include evaluation of safety (adverse events; effect on QTcF; immunogenicity), pharmacokinetics, efficacy, pharmacodynamics, and determination of recommended Phase 2 doses. As of 25 January 2016, 9 pts have enrolled in part A. The first four dose cohorts were safe and well tolerated. The study is expected to recruit approximately 100–120 pts in total. Clinical trial information: EudraCT 2014-004896-22.