title: Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients.
abstract: Whereas the chimeric type I anti-CD20 Ab rituximab has improved outcomes for patients with B-cell malignancies significantly, many patients with non-Hodgkin lymphoma (NHL) remain incurable. Obinutuzumab (GA101) is a glycoengineered, humanized anti-CD20 type II Ab that has demonstrated superior activity against type I Abs in vitro and in preclinical studies. In the present study, we evaluated the safety, efficacy, and pharmacokinetics of GA101 in a phase 1 study of 21 patients with heavily pretreated, relapsed, or refractory CD20(+) indolent NHL. Patients received GA101 in a dose-escalating fashion (3 per cohort, range 50/100-1200/2000 mg) for 8 × 21-day cycles. The majority of adverse events (AEs) were grades 1 and 2 (114 of 132 total AEs). Seven patients reported a total of 18 grade 3 or 4 AEs. Infusion-related reactions were the most common AE, with most occurring during the first infusion and resolving with appropriate management. Three patients experienced grade 3 or 4 drug-related infusion-related reactions. The best overall response was 43%, with 5 complete responses and 4 partial responses. Data from this study suggest that GA101 was well tolerated and demonstrated encouraging activity in patients with previously treated NHL up to doses of 2000 mg. This trial is registered at www.clinicaltrials.gov as NCT00517530.
authors.affiliation: Hospices Civils de Lyon, Hematologie, Université de Lyon, Unité Mixte de Recherche (UMR) 5239, Centre National de la Recherche Scientifique (CNRS), Pierre-Bénite, France. gilles.salles@chu-lyon.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Salles
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauser
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.forename: Noel
authors.initials: N
authors.lastname: Milpied
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
authors.forename: Hervé
authors.initials: H
authors.lastname: Tilly
authors.forename: Gabi
authors.initials: G
authors.lastname: Bieska
authors.forename: Elina
authors.initials: E
authors.lastname: Asikanius
authors.forename: David
authors.initials: D
authors.lastname: Carlile
authors.forename: Joe
authors.initials: J
authors.lastname: Birkett
authors.forename: Pavel
authors.initials: P
authors.lastname: Pisa
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cartron
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects*; D018951:Antigens, CD20; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; C543332:obinutuzumab