Phase I and II clinical trials of trastuzumab

This report summarizes the efficacy of trastuzumab (Herceptin) based on its completed clinical trial program in patients with HER2-positive metastatic breast cancer for phase I and II studies which have been completed to date and were integral in the submission that led to approval of trastuzumab fo r clinical use in the USA. There were three small-scale, phase I clinical t rials conducted, which were primarily designed to determine the safety and pharmacokinetics of trastuzumab (10-500 mg) administered i.v. as single or weekly doses. This was followed by two phase II clinical trials of fixed-do se trastuzumab either as a single-agent or in combination with cisplatin in 46 and 39 patients, which produced overall response rates of 11.6% and 24. 3%, respectively. In a pivotal phase II clinical trial, trastuzumab was adm inistered on a bodyweight-adjusted basis as a single agent to 222 patients with HER2-positive metastatic breast cancer who had relapsed after one or t wo prior chemotherapy regimens. The overall response rate was 21% when asse ssed in evaluable patients by the investigators and 15% when analyzed on an intent-to-treat basis by an independent Response Evaluation Committee. The pharmacokinetics of trastuzumab were evaluated in these studies and the re sults are summarized.