Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies
Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q...
Ausführliche Beschreibung
Autor*in: |
Aung Naing [verfasserIn] Jeffrey Infante [verfasserIn] Sanjay Goel [verfasserIn] Howard Burris [verfasserIn] Chelsea Black [verfasserIn] Shannon Marshall [verfasserIn] Ikbel Achour [verfasserIn] Susannah Barbee [verfasserIn] Rena May [verfasserIn] Chris Morehouse [verfasserIn] Kristen Pollizzi [verfasserIn] Xuyang Song [verfasserIn] Keith Steele [verfasserIn] Nairouz Elgeioushi [verfasserIn] Farzana Walcott [verfasserIn] Joyson Karakunnel [verfasserIn] Patricia LoRusso [verfasserIn] Amy Weise [verfasserIn] Joseph Eder [verfasserIn] Brendan Curti [verfasserIn] Michael Oberst [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2019 |
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In: Journal for ImmunoTherapy of Cancer - BMJ Publishing Group, 2013, 7(2019), 1, Seite 15 |
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Übergeordnetes Werk: |
volume:7 ; year:2019 ; number:1 ; pages:15 |
Links: |
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DOI / URN: |
10.1186/s40425-019-0665-2 |
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Katalog-ID: |
DOAJ002219565 |
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520 | |a Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. | ||
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650 | 4 | |a Kidney cancer | |
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653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
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10.1186/s40425-019-0665-2 doi (DE-627)DOAJ002219565 (DE-599)DOAJcf9d82e0ebcd4aaeac76ef9a975cf4f7 DE-627 ger DE-627 rakwb eng RC254-282 Aung Naing verfasserin aut Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. MEDI0680 PD-1 Immunotherapy Kidney cancer Melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jeffrey Infante verfasserin aut Sanjay Goel verfasserin aut Howard Burris verfasserin aut Chelsea Black verfasserin aut Shannon Marshall verfasserin aut Ikbel Achour verfasserin aut Susannah Barbee verfasserin aut Rena May verfasserin aut Chris Morehouse verfasserin aut Kristen Pollizzi verfasserin aut Xuyang Song verfasserin aut Keith Steele verfasserin aut Nairouz Elgeioushi verfasserin aut Farzana Walcott verfasserin aut Joyson Karakunnel verfasserin aut Patricia LoRusso verfasserin aut Amy Weise verfasserin aut Joseph Eder verfasserin aut Brendan Curti verfasserin aut Michael Oberst verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 7(2019), 1, Seite 15 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/article/cf9d82e0ebcd4aaeac76ef9a975cf4f7 kostenfrei http://link.springer.com/article/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15 |
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10.1186/s40425-019-0665-2 doi (DE-627)DOAJ002219565 (DE-599)DOAJcf9d82e0ebcd4aaeac76ef9a975cf4f7 DE-627 ger DE-627 rakwb eng RC254-282 Aung Naing verfasserin aut Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. MEDI0680 PD-1 Immunotherapy Kidney cancer Melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jeffrey Infante verfasserin aut Sanjay Goel verfasserin aut Howard Burris verfasserin aut Chelsea Black verfasserin aut Shannon Marshall verfasserin aut Ikbel Achour verfasserin aut Susannah Barbee verfasserin aut Rena May verfasserin aut Chris Morehouse verfasserin aut Kristen Pollizzi verfasserin aut Xuyang Song verfasserin aut Keith Steele verfasserin aut Nairouz Elgeioushi verfasserin aut Farzana Walcott verfasserin aut Joyson Karakunnel verfasserin aut Patricia LoRusso verfasserin aut Amy Weise verfasserin aut Joseph Eder verfasserin aut Brendan Curti verfasserin aut Michael Oberst verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 7(2019), 1, Seite 15 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/article/cf9d82e0ebcd4aaeac76ef9a975cf4f7 kostenfrei http://link.springer.com/article/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15 |
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10.1186/s40425-019-0665-2 doi (DE-627)DOAJ002219565 (DE-599)DOAJcf9d82e0ebcd4aaeac76ef9a975cf4f7 DE-627 ger DE-627 rakwb eng RC254-282 Aung Naing verfasserin aut Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. MEDI0680 PD-1 Immunotherapy Kidney cancer Melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jeffrey Infante verfasserin aut Sanjay Goel verfasserin aut Howard Burris verfasserin aut Chelsea Black verfasserin aut Shannon Marshall verfasserin aut Ikbel Achour verfasserin aut Susannah Barbee verfasserin aut Rena May verfasserin aut Chris Morehouse verfasserin aut Kristen Pollizzi verfasserin aut Xuyang Song verfasserin aut Keith Steele verfasserin aut Nairouz Elgeioushi verfasserin aut Farzana Walcott verfasserin aut Joyson Karakunnel verfasserin aut Patricia LoRusso verfasserin aut Amy Weise verfasserin aut Joseph Eder verfasserin aut Brendan Curti verfasserin aut Michael Oberst verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 7(2019), 1, Seite 15 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/article/cf9d82e0ebcd4aaeac76ef9a975cf4f7 kostenfrei http://link.springer.com/article/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15 |
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10.1186/s40425-019-0665-2 doi (DE-627)DOAJ002219565 (DE-599)DOAJcf9d82e0ebcd4aaeac76ef9a975cf4f7 DE-627 ger DE-627 rakwb eng RC254-282 Aung Naing verfasserin aut Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. MEDI0680 PD-1 Immunotherapy Kidney cancer Melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jeffrey Infante verfasserin aut Sanjay Goel verfasserin aut Howard Burris verfasserin aut Chelsea Black verfasserin aut Shannon Marshall verfasserin aut Ikbel Achour verfasserin aut Susannah Barbee verfasserin aut Rena May verfasserin aut Chris Morehouse verfasserin aut Kristen Pollizzi verfasserin aut Xuyang Song verfasserin aut Keith Steele verfasserin aut Nairouz Elgeioushi verfasserin aut Farzana Walcott verfasserin aut Joyson Karakunnel verfasserin aut Patricia LoRusso verfasserin aut Amy Weise verfasserin aut Joseph Eder verfasserin aut Brendan Curti verfasserin aut Michael Oberst verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 7(2019), 1, Seite 15 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/article/cf9d82e0ebcd4aaeac76ef9a975cf4f7 kostenfrei http://link.springer.com/article/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15 |
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10.1186/s40425-019-0665-2 doi (DE-627)DOAJ002219565 (DE-599)DOAJcf9d82e0ebcd4aaeac76ef9a975cf4f7 DE-627 ger DE-627 rakwb eng RC254-282 Aung Naing verfasserin aut Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. MEDI0680 PD-1 Immunotherapy Kidney cancer Melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Jeffrey Infante verfasserin aut Sanjay Goel verfasserin aut Howard Burris verfasserin aut Chelsea Black verfasserin aut Shannon Marshall verfasserin aut Ikbel Achour verfasserin aut Susannah Barbee verfasserin aut Rena May verfasserin aut Chris Morehouse verfasserin aut Kristen Pollizzi verfasserin aut Xuyang Song verfasserin aut Keith Steele verfasserin aut Nairouz Elgeioushi verfasserin aut Farzana Walcott verfasserin aut Joyson Karakunnel verfasserin aut Patricia LoRusso verfasserin aut Amy Weise verfasserin aut Joseph Eder verfasserin aut Brendan Curti verfasserin aut Michael Oberst verfasserin aut In Journal for ImmunoTherapy of Cancer BMJ Publishing Group, 2013 7(2019), 1, Seite 15 (DE-627)750086335 (DE-600)2719863-7 20511426 nnns volume:7 year:2019 number:1 pages:15 https://doi.org/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/article/cf9d82e0ebcd4aaeac76ef9a975cf4f7 kostenfrei http://link.springer.com/article/10.1186/s40425-019-0665-2 kostenfrei https://doaj.org/toc/2051-1426 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 15 |
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Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies |
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Aung Naing Jeffrey Infante Sanjay Goel Howard Burris Chelsea Black Shannon Marshall Ikbel Achour Susannah Barbee Rena May Chris Morehouse Kristen Pollizzi Xuyang Song Keith Steele Nairouz Elgeioushi Farzana Walcott Joyson Karakunnel Patricia LoRusso Amy Weise Joseph Eder Brendan Curti Michael Oberst |
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Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies |
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Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. |
abstractGer |
Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. |
abstract_unstemmed |
Abstract Background The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. Methods MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. Results Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. Conclusions MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. Trial registration NCT02013804; date of registration December 12, 2013. |
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Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies |
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Jeffrey Infante Sanjay Goel Howard Burris Chelsea Black Shannon Marshall Ikbel Achour Susannah Barbee Rena May Chris Morehouse Kristen Pollizzi Xuyang Song Keith Steele Nairouz Elgeioushi Farzana Walcott Joyson Karakunnel Patricia LoRusso Amy Weise Joseph Eder Brendan Curti Michael Oberst |
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