A phase I study of dacetuzumab (SGN-40, a humanized anti-CD40 monoclonal antibody) in patients with chronic lymphocytic leukemia

Abstract

Despite advances in therapy, chronic lymphocytic leukemia remains an incurable disease and novel, effective therapies are needed. In this open-label, dose-escalation, phase I study, dacetuzumab (IgG1 humanized monoclonal antibody) was administered to 12 adults, all of whom had received several prior systemic therapies (median, 4; range, 2–11). Intrapatient dose escalation (maximum weekly doses of 3–8 mg/kg) was used to diminish first-dose-related inflammatory symptoms. No dose-limiting toxicities or dose-dependent trends in adverse events (AEs) were observed. The most common AEs (in ≥2 patients) were fatigue, headache, anorexia, conjunctivitis, hyperhidrosis, and night sweats, all of which were mild or moderate. No deaths, serious AEs, or discontinuations due to AEs occurred. Although no patient achieved an objective response, five patients demonstrated stable disease after 1 cycle of therapy, with no discernable correlation between dacetuzumab dose and outcome. This modest single-agent activity may warrant further testing of dacetuzumab in combination with other chronic lymphocytic leukemia therapies.

Keywords:

• Chronic lymphocytic leukemia
• CD40
• monoclonal antibody
• SGN-40
• dacetuzumab
• clinical trial

Acknowledgements

The authors thank all the physicians, research staff, and patients who participated to this study, as well as Dr. Mark Goodman at University of Miami and Dr. David Maloney at Fred Hutchinson Cancer Research Center for their contributions to the study design and conduct. The authors also thank Hong Ren, Kate Harrop, Natalie Masterton, and Nancy Whiting of Seattle Genetics, Inc. for their assistance with the clinical study, and Linda Melvin for writing support. This study was registered at www.ClinicalTrials.gov with the identifier NCT00283101.

Declaration of Interest: This study was supported by the Seattle Genetics, Inc. R. R. Furman, A. Forero-Torres, and A. Shustov were investigators whose sites were funded to do this study. J.G. Drachman is an employee and has ownership interest in Seattle Genetics, Inc.