title: Phase I study of the humanized anti-CD40 monoclonal antibody dacetuzumab in refractory or recurrent non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics, and antitumor activity of dacetuzumab in patients with refractory or recurrent B-cell non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  In this open-label, dose-escalation phase I study, dacetuzumab was administered to six cohorts of adult patients. In the first cohort, patients received 2 mg/kg weekly for 4 weeks; in all other cohorts, an intrapatient dose-escalation schedule was used with increasing doses up to a maximum of 8 mg/kg. Patients with clinical benefit after one cycle of dacetuzumab were eligible for a second cycle.
  
  
  RESULTS
  In the 50 patients who received dacetuzumab, no dose dependence of adverse events (AEs) was observed. The most common AEs in >or= 20% of patients were fatigue, pyrexia, and headache; most were grade 1 or 2. Noninfectious inflammatory eye disorders occurred in 12% of patients. AEs grade >or= 3 occurred in 30% of patients and included disease progression, anemia, pleural effusion, and thrombocytopenia. Most laboratory abnormalities were grade 1 or 2; transient elevated hepatic aminotransferases occurred in 52% of patients. Two patients experienced dose-limiting toxicity: grade 3 conjunctivitis and transient vision loss in cohort (1), and grade 3 ALT elevation in cohort IV. The MTD of dacetuzumab was not established at the dose levels tested. Six objective responses were reported (one complete response, five partial responses). Tumor size decreased in approximately one third of patients.
  
  
  CONCLUSIONS
  Dacetuzumab monotherapy was well tolerated in patients with NHL in doses up to 8 mg/kg/wk. Preliminary response data are encouraging and support additional studies of dacetuzumab in this patient population.
authors.affiliation: Division of Oncology, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305, USA. radvani@stanford.edu
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.forename: Andres
authors.initials: A
authors.lastname: Forero-Torres
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Rosenblatt
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Kate
authors.initials: K
authors.lastname: Harrop
authors.forename: Nancy
authors.initials: N
authors.lastname: Whiting
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Drachman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D019013:CD40 Antigens / Q000276:immunology*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019013:CD40 Antigens; D016207:Cytokines; C543331:dacetuzumab