YM BioSciences Inc., an oncology company that identifies, develops and commercialises differentiated products for patients worldwide, has announced that the independent Data Safety Monitoring Board (DSMB) for the pivotal phase III trial of tesmilifene in patients with metastatic or recurrent breast cancer has completed its third planned safety and efficacy analysis.
The DSMB advised the company to stop the trial based on an interim analysis of 351 events, indicating it is very unlikely significant differences in overall survival will be shown between treatment arms as the data mature. The trial was not stopped due to safety concerns relating to the product. The company plans to submit data from this trial to an appropriate medical meeting after it completes its review.
Dr Joyce A O'Shaughnessy, a leading breast cancer researcher, oncologist and the designated safety officer of the DSMB, and Professor Lee-Jen, chair and statistician of the DEC trial DSMB stated that, "We extend high praise to YM BioSciences. The DSMB is of the opinion that the trial was well-conducted and well-executed."
The pivotal phase III trial compared the survival of patients treated with tesmilifene combined with epirubicin/cyclophosphamide to epirubicin/cyclophosphamide alone in women with rapidly progressing metastatic and/or recurrent breast cancer. The study, which completed enrolment of 723 patients in September 2005, was the subject of a special protocol assessment and a fast track designation for advanced breast cancer by the US Food and Drug Administration (FDA).
"We are very disappointed by this outcome and will be evaluating the data to understand why tesmilifene did not add a clinical benefit in this trial," said, David Allan, chairman and CEO of YM BioSciences. "Upon completing the review of the phase III data, the company will consider its options relating to tesmilifene.
In the meantime, we are fortunate to have two other late-stage products, which we expect to make important progress this year. Nimotuzumab is our humanized antibody targeting the epidermal growth factor receptor and has shown a more favourable safety profile in studies to date than currently approved products in that family. We also have AeroLEF, an inhaled composition of free and liposome-encapsulated fentanyl, which is unique in its ability to enable patients to individualize their dose to their pain level."
The trial was conducted according to a sequential design that permitted a number of planned interim analyses while the trial continued until one of two specific statistical conditions was satisfied. At each analysis, survival for the tesmilifene-containing treatment arm and the control arm was calculated and then reviewed by the DSMB. The trial was to be concluded if either the tesmilifene-containing treatment arm was superior to the control by a specified margin or it was determined that such evidence was not going to be found. After the third planned analysis, the DSMB concluded that the trial was highly unlikely to achieve a pre-specified survival benefit.
Tesmilifene is a novel, small molecule that selectively targets multiple-drug resistant (MDR) tumour cells, sensitising them to chemotherapy.