The University of Southampton
University of Southampton Institutional Repository

Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer

Pienta, Kenneth J., Machiels, Jean-Pascal, Schrijvers, Dirk, Alekseev, Boris, Shkolnik, Mikhail, Crabb, Simon J., Li, Susan, Seetharam, Shobha, Puchalski, Thomas A., Takimoto, Chris, Elsayed, Yusri, Dawkins, Fitzroy and de Bono, Johann S. (2012) Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer Investigational New Drugs (doi:10.1007/s10637-012-9869-8). (PMID:22907596).

Record type: Article

Abstract

Background CC-chemokine ligand 2 (CCL2) promotes tumor growth by angiogenesis, macrophage infiltration and tumor invasion, and distant metastasis. Carlumab (CNTO 888) is a human IgG(1)? mAb with high affinity and specificity for human CCL2. Preclinical data suggest carlumab may offer clinical benefit to cancer patients. Methods In a phase 2, open-label study, patients with metastatic castration-resistant prostate cancer (CRPC) previously treated with docetaxel received a 90-min infusion of 15 mg/kg carlumab q2w. The primary endpoint was response rate: change from baseline in skeletal lesions, extraskeletal lesions, and PSA values. Secondary endpoints included overall response rate (CR + PR) by RECIST, OS, PSA response, safety, pharmacodynamics, pharmacokinetics, immunogenicity. Results Forty-six patients were treated with 6 median (range 1, 26) doses. One patient had SD >6 months. There were no PSA or RECIST responses. Fourteen (34 %) patients had SD ?3 months. Median OS was 10.2 (95 % CI: 5.2, not estimable) months. Twelve (39 %) patients reported improved pain scores. AEs occurred in 43 (93 %) patients, including 27 (59 %) with grade ?3 AEs. Common grade ?3 AEs were back (11 %) and bone (9 %) pain. Twenty (43 %) patients experienced SAEs, including pneumonia, spinal cord compression, back pain. No patient developed antibodies to carlumab. Steady-state serum concentrations were achieved after 3 repeated doses and were above the 10-?g/mL target concentration. Suppression of free CCL2 serum concentrations was briefly observed following each dose but was not sustained. Conclusion Carlumab was well-tolerated but did not block the CCL2/CCR2 axis or show antitumor activity as a single agent in metastatic CRPC.

Full text not available from this repository.

More information

e-pub ahead of print date: 21 August 2012
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 342452
URI: http://eprints.soton.ac.uk/id/eprint/342452
ISSN: 0167-6997
PURE UUID: 7334f1cc-0bb1-4628-95bc-6a01037ab0c5

Catalogue record

Date deposited: 30 Aug 2012 09:07
Last modified: 18 Jul 2017 05:28

Export record

Altmetrics

Contributors

Author: Kenneth J. Pienta
Author: Jean-Pascal Machiels
Author: Dirk Schrijvers
Author: Boris Alekseev
Author: Mikhail Shkolnik
Author: Simon J. Crabb
Author: Susan Li
Author: Shobha Seetharam
Author: Thomas A. Puchalski
Author: Chris Takimoto
Author: Yusri Elsayed
Author: Fitzroy Dawkins
Author: Johann S. de Bono

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×