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

Ranjana Advani; Andres Forero-Torres; Richard R Furman; Joseph D Rosenblatt; Anas Younes; Hong Ren; Kate Harrop; Nancy Whiting; Jonathan G Drachman

doi:10.1200/JCO.2008.21.3017

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

Journal article

Peer reviewed

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

Ranjana Advani, Andres Forero-Torres, Richard R Furman, Joseph D Rosenblatt, Anas Younes, Hong Ren, Kate Harrop, Nancy Whiting and Jonathan G Drachman

Journal of clinical oncology, Vol.27(26), pp.4371-4377

2009-09-10

DOI: https://doi.org/10.1200/JCO.2008.21.3017

PMID: 19636010

Abstract

PurposeTo 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 MethodsIn 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.ResultsIn 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.ConclusionDacetuzumab 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.

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Collaboration types: Industry collaboration; Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.130 Lymphomas; 1.130.132 Lymphoma
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Phase I Study of the Humanized Anti-CD40 Monoclonal Antibody Dacetuzumab in Refractory or Recurrent Non-Hodgkin's Lymphoma
Creators: Ranjana Advani - 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
Andres Forero-Torres - 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
Richard R Furman - 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
Joseph D Rosenblatt - 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
Anas Younes - 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
Hong Ren - 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
Kate Harrop - 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
Nancy Whiting - 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
Jonathan G Drachman - 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
Publication Details: Journal of clinical oncology, Vol.27(26), pp.4371-4377
Academic Unit: Miller School of Medicine; UMMG Dept of Medicine - Hematology/Oncology
Language: English
Resource Type: Journal article
PMID: 19636010
Record Identifier: 991031598604002976