Pharmacokinetics and safety of subcutaneous nivolumab: results from the phase I/II CheckMate 8KX study

作者：Sara Lonardi, Iwona Ługowska, Anne O’Donnell, Christopher Jackson, Loes Maria Latten-Jansen, Richard North, Rastislav Bahleda, Marcelo Garrido, Armando Santoro, Matías Chacón, Linghui Li, Devanand Joseph, Heather Vezina, Urvi Aras, Bryan Bennett, Deepak Perumal, Balmeet Gurm, Wee-Teck Ng, R. Donald Harvey, José Trigo, Aitana Calvo · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2025-011918 · 被引用次数：2 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、HER2/EGFR in Cancer Research

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...