A Randomized Phase I Pharmacokinetic Trial Comparing The Potential Biosimilar Trastuzumab (Sibp-01) With The Reference Product (Herceptin (R)) In Healthy Chinese Male Volunteers

Objectives This study aimed to evaluate the bioequivalence, safety, tolerability and immunogenicity of the biosimilar trastuzumab (SIBP-01) compared to Herceptin (R). Methods In this Phase I randomized double-blind parallel-group trial, 100 healthy male volunteers were randomized in a1:1 ratio to receive a single 6 mg center dot kg-1 intravenous dose of SIBP-01 or Herceptin (R). Serum concentrationswere analyzed using a validated ELISA. Results The two groups had similar baseline characteristics. The geometric mean ratios (90% CI) of C-max, AUC(0-t)and AUC(inf)between the trial group and the reference group were 93.55%-104.27%, 91.98%-102.35% and 91.88%-102.34%, respectively; the geometric mean ratios (90% CI) of AUC(0-t)and AUC(inf)in the sensitivity analysis were 92.29%-102.63% and 91.81%-102.16%, respectively. These values were within the prespecified equivalence margins, establishing the bioequivalence of SIBP-1 and Herceptin (R). AEs were similar across all subjects in the SIBP-01 and Herceptin (R) arms, with treatment-related AEs reported by 72.00% and 80.00%, respectively. In each group, there was one AE that caused a subject to discontinue the study. Expert opinion Trastuzumab (Herceptin (R)) is significantly more effective than chemotherapy in reducing exacerbations and tumor cell growth, and its adverse events are far lower than chemotherapy. Herceptin (R) is very expensive for most patients in China. The protein molecular primary structure of the biosimilar trastuzumab (SIBP-01) is consistent with Herceptin (R), with highly similar high level structure, biologocal activity and purity.But there are few studies comparing the bioequivalence of SIBP-01 and Herceptin (R) in healthy subjects and cancer patients. Conclusions This study showed the PK similarity of SIBP-01 to Herceptin (R). SIBP-01 was safe and well tolerated in healthy male volunteers, with no significant differences from the reference drug in safety or immunogenicity.