TY - JOUR
T1 - Phase I clinical study of RG7356, an anti-CD44 humanized antibody, in patients with acute myeloid leukemia
AU - Vey, Norbert
AU - Delaunay, Jacques
AU - Martinelli, Giovanni
AU - Fiedler, Walter
AU - Raffoux, Emmanuel
AU - Prebet, Thomas
AU - Gomez-Roca, Carlos
AU - Papayannidis, Cristina
AU - Kebenko, Maxim
AU - Paschka, Peter
AU - Christen, Randolph
AU - Guarin, Ernesto
AU - Bröske, Ann Marie
AU - Baehner, Monika
AU - Brewster, Michael
AU - Walz, Antje Christine
AU - Michielin, Francesca
AU - Runza, Valeria
AU - Meresse, Valerie
AU - Recher, Christian
PY - 2016/5/31
Y1 - 2016/5/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84973575909&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.8687
DO - 10.18632/oncotarget.8687
M3 - Journal articles
C2 - 27081038
AN - SCOPUS:84973575909
SN - 1949-2553
VL - 7
SP - 32532
EP - 32542
JO - Oncotarget
JF - Oncotarget
IS - 22
ER -