Results of a phase 1 study of AME-133v (LY2469298), an Fc-engineered humanized monoclonal anti-CD20 antibody, in FcγRIIIa-genotyped patients with previously treated follicular lymphoma.
OBJECTIVE
AME-133v is a humanized monoclonal antibody engineered to have increased affinity to CD20 and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) better than rituximab. Safety, pharmacokinetics, and efficacy were assessed in a phase 1/2 trial in patients with previously treated follicular lymphoma (FL).


METHODS
AME-133v was characterized in vitro by ADCC and cell binding assays. A phase 1 study was conducted in which 23 previously treated patients with FL were assigned sequentially to one of five dose-escalation cohorts of AME-133v at 2, 7.5, 30, 100, or 375 mg/m(2) weekly × 4 doses.


RESULTS
AME-133v showed a 13- to 20-fold greater binding affinity for CD20 and was 5- to 7-fold more potent than rituximab in ADCC assays. Cell binding assays showed AME-133v and rituximab competed for an overlapping epitope on the CD20 antigen, and AME-133v inhibited binding of biotinylated rituximab to CD20 in a concentration-dependent manner. AME-133v was well tolerated by patients and common related adverse events included chills and fatigue. One patient experienced a dose-limiting toxicity of neutropenia. AME-133v showed nonlinear pharmocokinetics with properties similar to rituximab. Selective reduction of B cells during and after AME-133v treatment was shown by flow cytometry of peripheral blood. A partial or complete response was observed in 5 of 23 (22%) patients and the median progression-free survival was 25.4 weeks.


CONCLUSIONS
AME-133v was safe and well tolerated at the doses tested. AME-133v showed encouraging results as an anti-CD20 therapy in heavily pretreated FL patients with the less favorable FcγRIIIa F-carrier genotype.
University of Alabama at Birmingham, Birmingham, Alabama, USA.
Andres
A
Forero-Torres
Sven
S
de Vos
Brad L
BL
Pohlman
Maksim
M
Pashkevich
Damien M
DM
Cronier
Nam H
NH
Dang
Susan P
SP
Carpenter
Barrett W
BW
Allan
James G
JG
Nelson
Christopher A
CA
Slapak
Mitchell R
MR
Smith
Brian K
BK
Link
James E
JE
Wooldridge
Kristen N
KN
Ganjoo
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C496124:FCGR3A protein, human; D017452:Receptors, IgG; C550337:ocaratuzumab