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cancer, article, prostate, google, scholar, pubmed, research, cas, ccl, metastatic, patients, clin, study, carlumab, castrationresistant, janssen, johnson, phase, human, cnto, pienta, bono, received, pain, oncol, privacy, cookies, content, data, monoclonal, antibody, ligand, puchalski, tumor, access, prednisone, res, development, usa, publish, search, ccchemokine, august, kenneth, schrijvers, takimoto, growth, docetaxel, response, bone,

Topics {✒️}

randomised open-label trial month download article/chapter cc-chemokine ligand 2 steady-state serum concentrations 10-μg/ml target concentration 15 mg/kg carlumab q2w pthrp-induced mcp-1 production metastatic prostate cancer consultant/advisory board member jean-pascal machiels progressive prostate cancer advanced prostate cancer prostate cancer growth open-label study prostate cancer progression randomized controlled trial full article pdf monocyte chemotactic protein-1 promotes tumor growth privacy choices/manage cookies received research grants offer clinical benefit related subjects autocrine factor human monoclonal antibody targeting ccl2 de bono ccr2 expression correlates metastatic bone disease patient developed antibodies prostate cancer single agent cancer research human igg1κ mab check access instant access article investigational european economic area secondary endpoints included spinal cord compression show antitumor activity prostatic hyperplasia destructive cascade mediated world health organization nhs foundation trust conditions privacy policy ccl2/ccr2 axis response evaluation criteria accepting optional cookies shobha seetharam

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         headline:Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer
         description: 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.
         datePublished:2012-08-21T00:00:00Z
         dateModified:2012-08-21T00:00:00Z
         pageStart:760
         pageEnd:768
         sameAs:https://doi.org/10.1007/s10637-012-9869-8
         keywords:
            Prostatic neoplasms
            CC chemokine ligand 2
            Carlumab
            CC chemokine receptor 2
            Oncology
            Pharmacology/Toxicology
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      headline:Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer
      description: 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.
      datePublished:2012-08-21T00:00:00Z
      dateModified:2012-08-21T00:00:00Z
      pageStart:760
      pageEnd:768
      sameAs:https://doi.org/10.1007/s10637-012-9869-8
      keywords:
         Prostatic neoplasms
         CC chemokine ligand 2
         Carlumab
         CC chemokine receptor 2
         Oncology
         Pharmacology/Toxicology
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