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;de Bono, Johann S;et.al.
(2012) Investigational New Drugs : the journal of new anti-cancer agents — Vol. 31, n° 3, p. 760-768 (2012)

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Authors
  • Pienta, Kenneth J
    Author
  • Machiels, Jean-PascalUCLouvain
    Author
  • Schrijvers, Dirk
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  • Alekseev, Boris
    Author
  • de Bono, Johann S
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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)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.
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Pienta, K. J., Machiels, J.-P., Schrijvers, D., Alekseev, B., Shkolnik, M., Crabb, S. J., Li, S., Seetharam, S., Puchalski, T. A., Takimoto, C., Elsayed, Y., Dawkins, F., & de Bono, J. 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 : the journal of new anti-cancer agents, 31(3), 760-768. https://doi.org/10.1007/s10637-012-9869-8 (Original work published 2012)