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J Hematol Oncol. 2014 Jun 12;7:44. doi: 10.1186/1756-8722-7-44.

A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors.

Author information

1
David Geffen School of Medicine at UCLA, University of California Los Angeles, 650 Charles E, Young Drive 11-934 Factor Bldg, Los Angeles, CA 90095-1678, USA. deVos@mednet.ucla.edu.

Abstract

BACKGROUND:

Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study.

METHODS:

A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies.

RESULTS:

Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3-4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3-4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity.

CONCLUSIONS:

Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier NCT00435916.

PMID:
24919462
PMCID:
PMC4065310
DOI:
10.1186/1756-8722-7-44
[Indexed for MEDLINE]
Free PMC Article

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