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 IgG1κ 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.
Prostatic neoplasms CC chemokine ligand 2 Carlumab CC chemokine receptor 2
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This study was sponsored by Janssen Research & Development. The following investigators participated in the study: UK: Christian Ottensmeier, Janet Brown, Nicholas D. James; US: George Giels. The authors thank Bob Zhong of Janssen Research & Development for his involvement with the statistical design of the study and for critical review of the manuscript and Jennifer Han of Janssen Services, LLC for assistance in writing and preparing the manuscript.
Conflicts of interest
Kenneth J. Pienta has received research grants from and been a consultant for Centocor B.V. Dirk Schrijvers has received commercial research grants from Cougar, Johnson & Johnson, and Janssen Pharmaceuticals. Boris Alekseev has received commercial research grants. Susan Li, Shobha Seetharam, Thomas A. Puchalski, Chris Takimoto, Yusri Elsayed, and Fitzroy Dawkins are employees of Janssen, a subsidiary of Johnson & Johnson, and own Johnson & Johnson stock options. Johann S. de Bono has received honoraria and been a consultant/advisory board member for Johnson & Johnson.
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