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A phase 1 study of lucatumumab, a fully human anti‐ CD 40 antagonist monoclonal antibody administered intravenously to patients with relapsed or refractory multiple myeloma
Author(s) -
Bensinger William,
Maziarz Richard T.,
Jagannath Sundar,
Spencer Andrew,
Durrant Simon,
Becker Pamela S.,
Ewald Brett,
Bilic Sanela,
Rediske John,
Baeck Johan,
Stadtmauer Edward A.
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2012.09251.x
Subject(s) - medicine , chills , adverse effect , refractory (planetary science) , pharmacokinetics , pharmacodynamics , gastroenterology , multiple myeloma , neutropenia , toxicity , physics , astrobiology
Summary In this open‐label, multicentre, phase 1 study a fully human anti‐ CD 40 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 ( DLT s). 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). DLT s 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.