Systems Medicine, LLC, a wholly-owned subsidiary of Cell Therapeutics, Inc. announced that its cancer drug candidate showed anti tumour activity in an early stage study.
The cumulative preliminary results of the phase I trial combining cisplatin with brostallicin, developed by Nerviano Medical Sciences, in patients with solid tumours that had relapsed or were resistant to front-line treatment were presented at the Highlights in Oncology meeting in Naples, Italy.
The trial is based on data demonstrating tumours with high levels of GSH/GST, common in platinum-resistant disease, are more susceptible to the killing effects of brostallicin. High levels of GSH and GST are associated with resistance to most standard chemotherapy drugs.
"Our phase I and II experience with brostallicin in over 160 patients demonstrates encouraging anti-tumour activity in a variety of solid tumours, with more than 50 per cent of the patients experiencing at least disease stabilization," said Steven Weitman, M.D., Systems Medicine.
The preliminary results from the first 21 patients treated in the phase I combination trial with cisplatin showed similar results, with 14 of the patients experiencing stable disease and half (50 per cent) of those 14 patients having durable stable disease for more than six cycles of therapy. Toxicities were mainly haematological and were manageable and reversible in this heavily pre-treated patient population. phase II studies using this combination in patients resistant to standard therapy are planned.
The phase I, multicenter, dose-escalation study of brostallicin in combination with cisplatin (cDDP) was conducted in patients with recurrent or metastatic solid tumours. Treatment cycles were three weeks. Brostallicin was escalated from 5 to 7 to 9 mg/m2 with a fixed dose of cDDP of 75 mg/m2.
Brostallicin, a novel synthetic second-generation DNA minor groove binder, has potent cancer killing activity and has demonstrated synergism in combination with standard cytotoxic agents as well as with newer targeted therapies in preclinical experimental tumours models. Brostallicin binds covalently to DNA within the DNA minor groove interfering with DNA division and leading to tumour cell death. More than 200 patients have been treated with brostallicin in single-agent and combination studies. Brostallicin had predictable and predominantly hematologic toxicities. Activity was demonstrated in a number of solid tumour types. A phase II study of brostallicin in relapsed/refractory soft tissue sarcoma met its pre-defined activity and safety hurdles and resulted in a first-line phase II study that is currently being conducted by the European Organization for Research and Treatment of Cancer (EORTC).
In July 2007, CTI acquired Systems Medicine (SM), a privately-held oncology company, in a stock-for-stock merger. SM applies a systems biology approach to drug development, combining pharmacogenomics and bioinformatics with experienced preclinical, clinical, and regulatory expertise to find and exploit a specific cancer's 'context of vulnerability.' Specifically, SM defines the molecular and genetic alterations (context) that cause cancer cells to be particularly sensitive (vulnerable) to a drug or combination of drugs the 'context of vulnerability'.