A phase 1 study of lucatumumab, a fully human anti-CD40 antagonist monoclonal antibody administered intravenously to patients with relapsed or refractory multiple myeloma

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.