A Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of A140 Injection and Cetuximab (Erbitux®) in Healthy Chinese Male Subjects

• Published in: Advances in therapy Vol. 42; no. 6; pp. 2797 - 2807
• Main Authors: Xu, Jia, Ge, Junyou, Li, Yaling, Liu, Shulin, Li, Sicong, Si, Jing, Liu, Juncheng, Zhu, Xiaoxue, Ding, Yanhua
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.06.2025
• Subjects: Adult; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - immunology; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - immunology; Antineoplastic Agents, Immunological - pharmacokinetics; Area Under Curve; Asian People; Cardiology; Cetuximab - administration & dosage; Cetuximab - adverse effects; Cetuximab - immunology; Cetuximab - pharmacokinetics; China; Double-Blind Method; East Asian People; Endocrinology; Healthy Volunteers; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Research; Pharmacology/Toxicology; Rheumatology; Therapeutic Equivalency; Young Adult; China; A140; Safety; Immunogenicity; Cetuximab; Pharmacokinetics
• ISSN: 0741-238X; 1865-8652; 1865-8652
• DOI: 10.1007/s12325-025-03193-9

Introduction This study aimed to compare the pharmacokinetic (PK) profiles, safety, and immunogenicity of the proposed A140 with those of cetuximab (Erbitux ® ) in healthy Chinese male subjects. Methods We conducted a randomized, single-dose, double-blind, parallel-controlled phase I study in which 82 healthy subjects were randomized equally into the A140 group and the cetuximab group. Both the test and comparator drug were administered as a single intravenous (IV) dose of 250 mg/m 2 . Blood samples were collected as per a designated schedule to evaluate PKs and immunogenicity. Safety was assessed throughout the study. PK similarity was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of the A140 to cetuximab for area under the concentration–time curve from time zero to the last measurable concentration (AUC 0– t ) were within the predefined bioequivalence range of 80–125%. Results The results showed that the 90% CI of the GMR for PK parameters (AUC 0– t , AUC 0–∞ , C max ) between the A140 and cetuximab groups were all within the predefined equivalent interval of 80–125%. Furthermore, the types of treatment-related adverse events were similar between the two groups, with an incidence of 100%. However, approximately 80% of these events belonged to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2. Anti-drug antibody (ADA) profiles were comparable between the A140 and the cetuximab group. Conclusion A140 demonstrated similar PK to cetuximab and comparable safety and immunogenicity in healthy Chinese male subjects. Trial Registration CTR20182229 ( https://www.chinadrugtrials.org.cn/ ).