Originally published as JCO Early Release 10.1200/JCO.2008.21.3017 on July 27 2009

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Phase I Study of the Humanized Anti-CD40 Monoclonal Antibody Dacetuzumab in Refractory or Recurrent Non-Hodgkin's Lymphoma

From the Division of Oncology, Stanford University Medical Center, Stanford, CA; Wallace Tumor Institute, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL; Division of Hematology/Oncology, Weill Cornell Medical Center, New York, NY; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL; M. D. Anderson Cancer Center, University of Texas, Houston, TX; Seattle Genetics Inc, Bothell, WA.

Corresponding author: Ranjana Advani, MD, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305; e-mail: radvani{at}stanford.edu.

Purpose 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).

Patients and 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 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 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.

Conclusion 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.

Supported by Seattle Genetics Inc.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL; the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA; the 47th Annual Meeting of the American Society of Hematology, December 10-13, 2005, Atlanta, GA; the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL; and the 10th International Conference on Malignant Lymphoma, June 4-7, 2008, Lugano, Switzerland.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00103779 [ClinicalTrials.gov] .

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