In this open-label, multicentre, phase 1 study a fully human anti-CD40 
antagonist monoclonal antibody, lucatumumab, was evaluated in patients with 
relapsed/refractory multiple myeloma (MM). The primary objective was to 
determine the maximum tolerated dose (MTD) based on dose-limiting toxicities 
(DLTs). Secondary objectives included safety, pharmacokinetics, pharmacodynamics 
and antimyeloma activity. Twenty-eight patients, enrolled using a standard 
'3 + 3' dose escalation, received one or two (n = 3) cycles of lucatumumab 1·0, 
3·0, 4·5 or 6·0 mg/kg once weekly for 4 weeks. Common lucatumumab-related 
adverse events were reversible, mild-to-moderate infusion reactions. Severe 
adverse events were anaemia, chills, hypercalcaemia and pyrexia (7% each). DLTs 
included grade 4 thrombocytopenia, grade 3 increased alanine aminotransferase 
and grade 4 increased lipase (n = 1 each). The MTD was 4·5 mg/kg. At doses 
≥3·0 mg/kg, sustained receptor occupancy (≥87%), observed throughout weekly 
infusions up to 5 weeks after the last infusion, correlated with an estimated 
half-life of 4-19 d. Twelve patients (43%) had stable disease, and one patient 
(4%) maintained a partial response for ≥8 months. These findings indicate that 
single-agent lucatumumab was well tolerated up to 4·5 mg/kg with modest clinical 
activity in relapsed/refractory MM, warranting further study as a combination 
therapy.