The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of
bivatuzumab mertansine in patients with CD44v6-positive metastatic
breast cancer.
Anthracycline and
taxane-pretreated patients with metastatic
breast cancer that expressed CD44v6 received one single infusion of
bivatuzumab mertansine and were observed for 21 days within one treatment course. Starting dose was 25 mg/m, while dose was escalated by increments of 25 mg/m. Patients who experienced a disease stabilization were eligible for further courses with
bivatuzumab mertansine. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis. Twenty-four patients were treated at eight different dose levels (25-200 mg/m), seven of these patients received more than one course of
bivatuzumab mertansine. Two dose-limiting toxicities occurred: one patient treated with 125 mg/m developed transient National Cancer Institute Common Toxicity Criteria grade 4 elevation of liver
enzymes; another patient treated at 175 mg/m experienced National Cancer Institute Common Toxicity Criteria grade 3
vomiting. She died from
renal failure, which might have been caused by deterioration of pre-existing
renal insufficiency. The most common toxicities were transient and mild skin disorders in 75% of patients. As a consequence of one fatal
toxic epidermal necrolysis that occurred in a study running in parallel, the clinical trials programme of
bivatuzumab mertansine was discontinued. None of the patients developed
antibodies against
bivatuzumab mertansine. No objective responses were observed. Disease stabilization was achieved in 50% of patients independently of dose level. In conclusion,
bivatuzumab mertansine targets CD44v6 and appears to stabilize heavily pretreated metastatic
breast cancer that expresses CD44v6. The maximum tolerated dose could not be determined in this trial as the sponsor discontinued the clinical development of
bivatuzumab mertansine.