Journal article
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
Clinical cancer research, Vol.18(5), pp.1395-1403
2012
DOI: 10.1158/1078-0432.CCR-11-0850
PMID: 22223529
Abstract
Purpose: 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).
Patients and 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.
Details
- Title: Subtitle
- 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
- Creators
- Andres FORERO-TORRES - University of Alabama at Birmingham, Birmingham, Alabama, United StatesSven DE VOS - David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United StatesMitchell R SMITH - Fox Chase Cancer Center, Philadelphia, Pennsylvania, United StatesBrian K LINK - Holden Comprehensive Cancer Center at University of Iowa, Iowa City, Iowa, United StatesJames E WOOLDRIDGE - Eli Lilly and Company, Indianapolis, Indiana, United StatesKristen N GANJOO - Stanford University Cancer Center, Palo Alto, California, United StatesBrad L POHLMAN - Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, United StatesMaksim PASHKEVICH - Eli Lilly and Company, Indianapolis, Indiana, United StatesDamien M CRONIER - Eli Lilly and Company, Windlesham, United KingdomNam H DANG - University of Florida, Gain-seville, Florida, United StatesSusan P CARPENTER - Applied Molecular Evolution, San Diego, California, United StatesBarrett W ALLAN - Applied Molecular Evolution, San Diego, California, United StatesJames G NELSON - Applied Molecular Evolution, San Diego, California, United StatesChristopher A SLAPAK - Eli Lilly and Company, Indianapolis, Indiana, United States
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.18(5), pp.1395-1403
- Publisher
- American Association for Cancer Research
- DOI
- 10.1158/1078-0432.CCR-11-0850
- PMID
- 22223529
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Language
- English
- Date published
- 2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094385602771
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