Phase I clinical study of RG7356, an anti-CD44 humanized antibody, in patients with acute myeloid leukemia

Norbert Vey*, Jacques Delaunay, Giovanni Martinelli, Walter Fiedler, Emmanuel Raffoux, Thomas Prebet, Carlos Gomez-Roca, Cristina Papayannidis, Maxim Kebenko, Peter Paschka, Randolph Christen, Ernesto Guarin, Ann Marie Bröske, Monika Baehner, Michael Brewster, Antje Christine Walz, Francesca Michielin, Valeria Runza, Valerie Meresse, Christian Recher

*Corresponding author for this work
45 Citations (Scopus)


RG7356, a recombinant anti-CD44 immunoglobulin G1 humanized monoclonal antibody, inhibits cell adhesion and has been associated with macrophage activation in preclinical models. We report results of a phase I dose-escalation study of RG7356 in relapsed/refractory acute myeloid leukemia (AML). Eligible patients with refractory AML, relapsed AML after induction chemotherapy, or previously untreated AML not eligible for intensive chemotherapy were enrolled and received intravenous RG7356 at dosages ≤ 2400 mg every other week or ≤ 1200 mg weekly or twice weekly; dose escalation started at 300 mg. Forty-four patients (median age, 69 years) were enrolled. One dose-limiting toxicity occurred (grade 3 hemolysis exacerbation) after one 1200 mg dose (twice-weekly cohort). The majority of adverse events were mild/moderate. Infusion-related reactions occurred in 64% of patients mainly during cycle 1. Two patients experienced grade 3 drug-induced aseptic meningitis. Pharmacokinetics increased supraproportionally, suggesting a target-mediated drug disposition (TMDD) at ≥ 1200 mg. Two patients achieved complete response with incomplete platelet recovery or partial response, respectively. One patient had stable disease with hematologic improvement. RG7356 was generally safe and well tolerated. Maximum tolerated dose was not reached, but saturation of TMDD was achieved. The recommended dose for future AML evaluations is 2400 mg every other week.

Original languageEnglish
Issue number22
Pages (from-to)32532-32542
Number of pages11
Publication statusPublished - 31.05.2016


Dive into the research topics of 'Phase I clinical study of RG7356, an anti-CD44 humanized antibody, in patients with acute myeloid leukemia'. Together they form a unique fingerprint.

Cite this