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).
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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)κ 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-μg/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.
|Subjects:||R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)|
|Divisions:||Faculty of Medicine > Cancer Sciences
|Date Deposited:||30 Aug 2012 09:07|
|Last Modified:||30 Aug 2012 09:07|
|Contributors:||Pienta, Kenneth J. (Author)
Machiels, Jean-Pascal (Author)
Schrijvers, Dirk (Author)
Alekseev, Boris (Author)
Shkolnik, Mikhail (Author)
Crabb, Simon J. (Author)
Li, Susan (Author)
Seetharam, Shobha (Author)
Puchalski, Thomas A. (Author)
Takimoto, Chris (Author)
Elsayed, Yusri (Author)
Dawkins, Fitzroy (Author)
de Bono, Johann S. (Author)
|Date:||21 August 2012|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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