TY - JOUR
T1 - Pharmacokinetics and safety of subcutaneous nivolumab
T2 - results from the phase I/II CheckMate 8KX study
AU - Lonardi, Sara
AU - Lugowska, Iwona
AU - O'Donnell, Anne
AU - Jackson, Christopher
AU - Latten-Jansen, Loes Maria
AU - North, Richard
AU - Bahleda, Rastislav
AU - Garrido, Marcelo
AU - Santoro, Armando
AU - Chacon, Matías Rodrigo
AU - Li, Linghui
AU - Joseph, Devanand
AU - Vezina, Heather E.
AU - Aras, Urvi
AU - Bennett, Bryan
AU - Perumal, Deepak
AU - Gurm, Balmeet
AU - Ng, Wee Teck
AU - Harvey, R. Donald
AU - Trigo, José
AU - Calvo, Aitana
N1 - Funding Information:
The authors sincerely thank all patients, their families, investigators, clinical trial researchers, personnel, and staff who contributed to the study. The authors also thank all Bristol Myers Squibb colleagues who made valuable contributions to the study. Medical writing was provided by Peter Harrison, PhD, Keri Wellington, PhD, and Caroline Charles, MD, PhD; editorial support was provided by Tina Allen, BSc, all of Spark (a division of Prime, New York, USA) (Link). This study was funded by Bristol Myers Squibb in accordance with Good Publication Practice guidelines. The sponsor was involved in the design of the study; in the collection, analysis, and interpretation of the data; in the writing of the manuscript; and in the decision to submit the manuscript for publication
Funding Information:
AC has received honoraria from Bristol Myers Squibb and MSD; support for attending meetings and/or travel from Daiichi Sankyo, MSD, and Novartis; and advisory board payments from Bristol Myers Squibb, MSD, and Eisai. AO\u2019D, AS, CJ, JT, LML-J, MRC, MG, RB, and RN declare no conflicts of interest. BB was an employee of Bristol Myers Squibb at the time of the study. BG, DJ, DP, HEV, LL, UA, and W-TN are employees of, and hold stock options in, Bristol Myers Squibb. I\u0141 has received research funding from AstraZeneca, BeiGene, Bristol Myers Squibb, Celon, Immunocore, MSD, Pfizer, Roche/Genentech, and RyVu. RDH has received institutional research funding from AbbVie, Amgen, AstraZeneca, Boston Biomedical, Eli Lilly, Genmab, GSK, Janssen, Meryx, Pfizer, Regeneron, Sanofi, and Xencor; and consulting fees from Amgen, EMD Serono, Erasca, and Genmab. SL has received honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre-Fabre, Roche, and Servier; and advisory board payments from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, GSK, Helion, Incyte, Lilly, Merck Serono, MSD, Nimbus Therapeutics, Rottapharm Servier, and Takeda.
Publisher Copyright:
© Author(s) (or their employer(s)) 2025.
PY - 2025/10/5
Y1 - 2025/10/5
N2 - 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. Trial registration number NCT03656718.
AB - 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. Trial registration number NCT03656718.
KW - immune checkpoint inhibitor
KW - immunotherapy
KW - pharmacokinetics - PK
KW - subcutaneous
U2 - 10.1136/jitc-2025-011918
DO - 10.1136/jitc-2025-011918
M3 - Article
SN - 2051-1426
VL - 13
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 10
M1 - e011918
ER -