Safety Assessment of an Anti-Müllerian Hormone Receptor II Therapeutic Antibody

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GM102 is a first-in-class glyco-engineered monoclonal antibody (mAb) targeting Anti-Müllerian Hormone Receptor II (AMHRII) and is in development for the treatment of gynecological cancers. The safety of GM102 was evaluated in mature female cynomolgus monkeys in a toxicity study with 4 cycles of intravenous administration (separated by 2 week intervals), at dose-levels of 30, 100 or 300 mg/kg. During the in vivo phase clinical investigations included cageside observations, rectal temperature, blood pressure, ECG and ophthalmology. Laboratory analyses included toxicokinetic profile, hematology, blood biochemistry, urinalysis, hormone assays (cortisol, estradiol, progesterone, anti-müllerian hormone), pro-inflammatory cytokines, anti-drug antibody (ADA) and Troponin I levels. At the end of the study, a complete histopathology evaluation was performed. No abnormalities related to the administration of GM102 were observed during the in vivo phase. Systemic exposure of GM102 at the highest dose-level was 318 563 ± 54 004 µg.h/mL (AUC_0-t) at the end of the treatment period. No effects were observed at hematology or blood biochemistry investigations. No abnormalities were observed in the hormone, Troponin I, cytokine or ADA measurements. At histopathology examinations, no adverse findings were recorded in GM102 treated animals. The highest tested dose‑level of 300 mg/kg was considered to be the No Observed Adverse Effect Level. These findings present a satisfactory safety profile of GM102 in view of its potential clinical use.