Inetetamab for injection in combination with vinorelbine weekly or every three weeks in HER2-positive metastatic breast cancer: A multicenter, randomized, phase II clinical trial.

Objective: We aimed to investigate the pharmacokinetics, safety, efficacy, and immunogenicity of different dosing regimens (weekly and every three weeks) of inetetamab in combination with vinorelbine in human epidermal growth factor receptor 2 (HER2)+ patients with metastatic breast cancer who had received one or more chemotherapy regimens.

Methods: HER2+ patients with metastatic breast cancer who had received one or more chemotherapy regimens were included. Eligible patients received inetetamab administered weekly or every three weeks in combination with vinorelbine injection chemotherapy. Pharmacokinetics, safety, efficacy, and immunogenicity were compared between the groups.

Results: Sixty HER2+ patients were randomized into a single-week administration group ( n = 29) and a three-week administration group ( n = 31). After the final dose in the single-week administration group and the three-week administration group, the mean C_max values were 79.773 μg/mL and 146.083 μg/mL; the mean C_min values were 30.227 μg/mL and 11.926 μg/mL; the mean AUC_tau values were 7328.443 μg·h/mL and 22647.101 μg·h/mL; and the mean C_av values were 43.622 μg/ mL and 44.935 μg/mL, respectively. The best overall response (BOR) rates at 24 weeks and unconfirmed BOR rates at 24 weeks were both 40.7% in the single-week dosing group and 40.7% in the three-week dosing group, and the 24-week confirmed disease control rates (DCRs) were 88.9% and 81.5%, respectively. The incidence of adverse events (AEs) was generally consistent across all levels.

Conclusion: There were slight differences in the mean C_max, C_min, AUC_tau and C_av between the three-week dosing group and the single-week dosing group, and the mean steady-state concentrations of C_av were comparable; however, there were no differences in efficacy, safety or immunogenicity between the two groups.