Sara Lonardi, Iwona Ługowska, Anne O'Donnell, Christopher Jackson, Loes Maria Latten-Jansen, Richard North, Rastislav Bahleda, Marcelo Garrido, Armando Santoro, Matías Rodrigo Chacon, Linghui Li, Devanand Joseph, Heather E Vezina, Urvi Aras, Bryan Bennett, Deepak Perumal, Balmeet Gurm, Wee-Teck Ng, R Donald Harvey, José Trigo, Aitana Calvo
{"title":"皮下纳武单抗的药代动力学和安全性：来自CheckMate 8KX I/II期研究的结果","authors":"Sara Lonardi, Iwona Ługowska, Anne O'Donnell, Christopher Jackson, Loes Maria Latten-Jansen, Richard North, Rastislav Bahleda, Marcelo Garrido, Armando Santoro, Matías Rodrigo Chacon, Linghui Li, Devanand Joseph, Heather E Vezina, Urvi Aras, Bryan Bennett, Deepak Perumal, Balmeet Gurm, Wee-Teck Ng, R Donald Harvey, José Trigo, Aitana Calvo","doi":"10.1136/jitc-2025-011918","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>CheckMate 8KX was a phase I/II study investigating the pharmacokinetics and safety of subcutaneous (SC) nivolumab±recombinant human hyaluronidase PH20 (rHuPH20).</p><p><strong>Methods: </strong>Patients with advanced solid tumors who were immune-checkpoint inhibitor-naïve were included. In parts A and B, patients received one single dose of nivolumab SC 720 mg or 960 mg±rHuPH20 2000 U/mL followed by nivolumab intravenous (IV) 480 mg every 4 weeks (Q4W). Patients receiving nivolumab IV could switch to nivolumab SC 1200 mg+rHuPH20 2000 U/mL Q4W in part C. Patients in part D received nivolumab SC 1200 mg+rHuPH20 Q4W. The primary objective was to describe the pharmacokinetics of nivolumab SC±rHuPH20. Secondary objectives included assessing safety and immunogenicity of nivolumab SC. Exploratory objectives included evaluating patient experience and preference and characterizing biomarker measures of immune function (pretreatment and on-treatment peripheral blood and tumor biopsies).</p><p><strong>Results: </strong>A total of 103 patients with various solid tumor types were treated between December 4, 2018 and September 7, 2022. Mean duration of injection was <5 min for nivolumab SC±rHuPH20. Nivolumab exposures over the first dosing interval increased with increasing dose; geometric-mean time to maximum concentration across doses was 117-167 hours (5-7 days). Nivolumab SC+rHuPH20 was well tolerated; grade 3/4 treatment-related adverse events occurred in 0%-11.1% of patients; antidrug antibodies were reported in some patients but were not associated with altered safety; no neutralizing antibodies were detected. Overall, patients preferred SC delivery over IV or had no preference. Increased tumor and peripheral pharmacodynamic biomarkers were observed postnivolumab SC, consistent with historical data for nivolumab IV.</p><p><strong>Conclusion: </strong>The pharmacokinetics of nivolumab SC have been well characterized and enabled dose selection for further study. Nivolumab SC has an acceptable safety profile, allows for rapid administration, and is preferred by more patients than nivolumab IV. These results encourage large-scale investigation of nivolumab SC.</p><p><strong>Trial registration number: </strong>NCT03656718.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 10","pages":""},"PeriodicalIF":10.6000,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506459/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics and safety of subcutaneous nivolumab: results from the phase I/II CheckMate 8KX study.\",\"authors\":\"Sara Lonardi, Iwona Ługowska, Anne O'Donnell, Christopher Jackson, Loes Maria Latten-Jansen, Richard North, Rastislav Bahleda, Marcelo Garrido, Armando Santoro, Matías Rodrigo Chacon, Linghui Li, Devanand Joseph, Heather E Vezina, Urvi Aras, Bryan Bennett, Deepak Perumal, Balmeet Gurm, Wee-Teck Ng, R Donald Harvey, José Trigo, Aitana Calvo\",\"doi\":\"10.1136/jitc-2025-011918\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>CheckMate 8KX was a phase I/II study investigating the pharmacokinetics and safety of subcutaneous (SC) nivolumab±recombinant human hyaluronidase PH20 (rHuPH20).</p><p><strong>Methods: </strong>Patients with advanced solid tumors who were immune-checkpoint inhibitor-naïve were included. In parts A and B, patients received one single dose of nivolumab SC 720 mg or 960 mg±rHuPH20 2000 U/mL followed by nivolumab intravenous (IV) 480 mg every 4 weeks (Q4W). Patients receiving nivolumab IV could switch to nivolumab SC 1200 mg+rHuPH20 2000 U/mL Q4W in part C. Patients in part D received nivolumab SC 1200 mg+rHuPH20 Q4W. The primary objective was to describe the pharmacokinetics of nivolumab SC±rHuPH20. Secondary objectives included assessing safety and immunogenicity of nivolumab SC. Exploratory objectives included evaluating patient experience and preference and characterizing biomarker measures of immune function (pretreatment and on-treatment peripheral blood and tumor biopsies).</p><p><strong>Results: </strong>A total of 103 patients with various solid tumor types were treated between December 4, 2018 and September 7, 2022. Mean duration of injection was <5 min for nivolumab SC±rHuPH20. Nivolumab exposures over the first dosing interval increased with increasing dose; geometric-mean time to maximum concentration across doses was 117-167 hours (5-7 days). Nivolumab SC+rHuPH20 was well tolerated; grade 3/4 treatment-related adverse events occurred in 0%-11.1% of patients; antidrug antibodies were reported in some patients but were not associated with altered safety; no neutralizing antibodies were detected. Overall, patients preferred SC delivery over IV or had no preference. Increased tumor and peripheral pharmacodynamic biomarkers were observed postnivolumab SC, consistent with historical data for nivolumab IV.</p><p><strong>Conclusion: </strong>The pharmacokinetics of nivolumab SC have been well characterized and enabled dose selection for further study. Nivolumab SC has an acceptable safety profile, allows for rapid administration, and is preferred by more patients than nivolumab IV. These results encourage large-scale investigation of nivolumab SC.</p><p><strong>Trial registration number: </strong>NCT03656718.</p>\",\"PeriodicalId\":14820,\"journal\":{\"name\":\"Journal for Immunotherapy of Cancer\",\"volume\":\"13 10\",\"pages\":\"\"},\"PeriodicalIF\":10.6000,\"publicationDate\":\"2025-10-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506459/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal for Immunotherapy of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jitc-2025-011918\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal for Immunotherapy of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jitc-2025-011918","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Pharmacokinetics and safety of subcutaneous nivolumab: results from the phase I/II CheckMate 8KX study.
Background: CheckMate 8KX was a phase I/II study investigating the pharmacokinetics and safety of subcutaneous (SC) nivolumab±recombinant human hyaluronidase PH20 (rHuPH20).
Methods: Patients with advanced solid tumors who were immune-checkpoint inhibitor-naïve were included. In parts A and B, patients received one single dose of nivolumab SC 720 mg or 960 mg±rHuPH20 2000 U/mL followed by nivolumab intravenous (IV) 480 mg every 4 weeks (Q4W). Patients receiving nivolumab IV could switch to nivolumab SC 1200 mg+rHuPH20 2000 U/mL Q4W in part C. Patients in part D received nivolumab SC 1200 mg+rHuPH20 Q4W. The primary objective was to describe the pharmacokinetics of nivolumab SC±rHuPH20. Secondary objectives included assessing safety and immunogenicity of nivolumab SC. Exploratory objectives included evaluating patient experience and preference and characterizing biomarker measures of immune function (pretreatment and on-treatment peripheral blood and tumor biopsies).
Results: A total of 103 patients with various solid tumor types were treated between December 4, 2018 and September 7, 2022. Mean duration of injection was <5 min for nivolumab SC±rHuPH20. Nivolumab exposures over the first dosing interval increased with increasing dose; geometric-mean time to maximum concentration across doses was 117-167 hours (5-7 days). Nivolumab SC+rHuPH20 was well tolerated; grade 3/4 treatment-related adverse events occurred in 0%-11.1% of patients; antidrug antibodies were reported in some patients but were not associated with altered safety; no neutralizing antibodies were detected. Overall, patients preferred SC delivery over IV or had no preference. Increased tumor and peripheral pharmacodynamic biomarkers were observed postnivolumab SC, consistent with historical data for nivolumab IV.
Conclusion: The pharmacokinetics of nivolumab SC have been well characterized and enabled dose selection for further study. Nivolumab SC has an acceptable safety profile, allows for rapid administration, and is preferred by more patients than nivolumab IV. These results encourage large-scale investigation of nivolumab SC.
期刊介绍：
The Journal for ImmunoTherapy of Cancer (JITC) is a peer-reviewed publication that promotes scientific exchange and deepens knowledge in the constantly evolving fields of tumor immunology and cancer immunotherapy. With an open access format, JITC encourages widespread access to its findings. The journal covers a wide range of topics, spanning from basic science to translational and clinical research. Key areas of interest include tumor-host interactions, the intricate tumor microenvironment, animal models, the identification of predictive and prognostic immune biomarkers, groundbreaking pharmaceutical and cellular therapies, innovative vaccines, combination immune-based treatments, and the study of immune-related toxicity.
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