YM BioSciences Inc announced that treatment has been started in its phase II trial combining tesmilifene with docetaxel (Taxotere). The trial is being conducted in collaboration with Sanofi-Aventis and will investigate the effect of this drug combination in women with rapidly progressing metastatic breast cancer.
The purpose of the study is to determine if the addition of tesmilifene to docetaxel has the potential to improve clinical response without increasing toxicity in patients. The primary endpoint of the trial is pharmacokinetic-assessing the effect of tesmilifene on the plasma concentration of docetaxel. YM anticipates enrollment will be completed in 2006 and that pharmacokinetic data will be available in early 2007. The secondary endpoints are overall survival and progression-free survival. Survival data from this trial will be compared to historical survival data for docetaxel alone.
"In the clinic, tesmilifene has been shown to significantly improve the effectiveness of commonly used cancer chemotherapies, prolonging survival when compared to chemotherapy alone," said Dr. Paul Keane, director of medical affairs at YM BioSciences. "Tesmilifene has been shown in both in vitro and in vivo preclinical models to allow the specific targeting of multiple drug-resistant cancer cells by anthracyclines, taxanes, vinca alkaloids, and cisplatin. These 'smart-targeting' effects allow the tesmilifene/cytotoxic combinations to destroy resistant cancer cells, the growth of nonresistant cells being retarded or eliminated by the inherent activity of the cytotoxic agents themselves."
The single-arm study is expected to enroll up to 39 women who are diagnosed with metastatic breast cancer or had their cancer recur within 24 months of their initial breast cancer diagnosis. Patients will be administered docetaxel every 21 days, and tesmilifene will be administered by a single infusion at the start of each docetaxel cycle. Following a five-patient dose escalation component, patients will be treated for up to 29 weeks unless there is evidence of unacceptable toxicity or disease progression. The study is being conducted in Europe and the United States.
"We expect to report survival data from this study in late 2007. While early analyses of data from our ongoing pivotal phase III trial will precede the conclusion of this phase II trial, a positive result in this trial would significantly broaden the commercial applicability of our lead drug," said David Allan, chairman and CEO of YM BioSciences.
Tesmilifene is a small-molecule drug currently undergoing a 700-patient pivotal phase III trial in metastatic and recurrent breast cancer that completed enrolment in 2005. The trial compares tesmilifene combined with epirubicin (Ellence)/cyclophosphamide against epirubicin/cyclophosphamide alone in women with rapidly progressing metastatic and recurrent breast cancer.
The trial is the subject of a Special Protocol Assessment by the US Food and Drug Administration (FDA) and is being conducted under an adaptive clinical design that provides three preplanned evaluations of the data, each of which could be sufficient for submission for marketing approval if the survival targets are achieved. The first interim analysis is expected to occur in mid-2006. YM has received FDA fast track designation for tesmilifene in advanced breast cancer.