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 for clinical use in the USA. There were three small-scale, phase I clinical trials 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-dose 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 administered on a bodyweight-adjusted basis as a single agent to 222 patients with HER2-positive metastatic breast cancer who had relapsed after one or two prior chemotherapy regimens. The overall response rate was 21% when assessed 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 results are summarized.