Format

Send to

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2013 Nov 15;19(22):6286-95. doi: 10.1158/1078-0432.CCR-13-1320. Epub 2013 Aug 27.

A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma.

Author information

1
Abramson Cancer Center; University of Pennsylvania, Philadelphia, PA.
2
Division of Hematology-Oncology, Department of Medicine.
3
Department of Radiology.
4
University of Washington, Seattle, WA.
5
Department of Biostatistics and Epidemiology.
6
University of Pittsburgh Cancer Institute, Pittsburgh, PA.
7
Abramson Family Cancer Research Institute.
#
Contributed equally

Abstract

PURPOSE:

This phase I study investigated the maximum-tolerated dose (MTD), safety, pharmacodynamics, immunologic correlatives, and antitumor activity of CP-870,893, an agonist CD40 antibody, when administered in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDA).

EXPERIMENTAL DESIGN:

Twenty-two patients with chemotherapy-naïve advanced PDA were treated with 1,000 mg/m(2) gemcitabine once weekly for three weeks with infusion of CP-870,893 at 0.1 or 0.2 mg/kg on day three of each 28-day cycle.

RESULTS:

CP-870,893 was well-tolerated; one dose-limiting toxicity (grade 4, cerebrovascular accident) occurred at the 0.2 mg/kg dose level, which was estimated as the MTD. The most common adverse event was cytokine release syndrome (grade 1 to 2). CP-870,893 infusion triggered immune activation marked by an increase in inflammatory cytokines, an increase in B-cell expression of costimulatory molecules, and a transient depletion of B cells. Four patients achieved a partial response (PR). 2-[(18)F]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) showed more than 25% decrease in FDG uptake within primary pancreatic lesions in six of eight patients; however, responses observed in metastatic lesions were heterogeneous, with some lesions responding with complete loss of FDG uptake, whereas other lesions in the same patient failed to respond. Improved overall survival correlated with a decrease in FDG uptake in hepatic lesions (R = -0.929; P = 0.007).

CONCLUSIONS:

CP-870,893 in combination with gemcitabine was well-tolerated and associated with antitumor activity in patients with PDA. Changes in FDG uptake detected on PET/CT imaging provide insight into therapeutic benefit. Phase II studies are warranted.

PMID:
23983255
PMCID:
PMC3834036
DOI:
10.1158/1078-0432.CCR-13-1320
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center