Cancer drug developer, Antisoma plc has started a phase-II trial evaluating the addition of AS1402 to the endocrine (hormonal) therapy letrozole in post-menopausal women receiving first-line treatment for advanced breast cancer.

Approximately 110 patients will be randomly assigned to receive either letrozole plus AS1402 or standard treatment with letrozole alone. The safety of the AS1402-letrozole combination will be evaluated and its efficacy compared with that of letrozole alone. Measures of efficacy will include response rates, time to tumour progression, progression-free survival and clinical benefit rate. Final results are expected in 2010.

The phase-II trial builds on a phase-I study in patients with heavily pre-treated breast cancer, which showed that AS1402 monotherapy was well-tolerated and was associated with prolonged stable disease in a number of patients.

AS1402 targets a cancer-associated form of the cell-surface protein MUC1. This form is found in approximately 90 per cent of breast cancers and in a wide range of other tumours. Tissue culture studies have shown that AS1402 binds to MUC1 on cancer cells and leads to their destruction by antibody-dependent cellular cytotoxicity (ADCC), a process involving recruitment of the immune system. Recent studies have shown that MUC1 up-regulates the oestrogen signalling pathway targeted by endocrine therapies. This provides a particular rationale for combining AS1402 with letrozole in Antisoma's phase-II trial.

Hospitals in the US, Russia, Ukraine, Poland and France are taking part in the phase-II study. The trial's principal investigator, Professor Nuhad Ibrahim, of the Anderson Cancer Center, University of Texas, said, "There is a clear rationale for testing AS1402 in this group of breast cancer patients, and we are pleased to be participating in this well-designed study."

Antisoma's chief operating officer, Dr Ursula Ney, added, "Worldwide, over 90,000 women each year receive endocrine treatment for advanced breast cancer, so many patients could benefit from any add-on therapy that improved outcomes in this setting. Our phase-II study rigorously tests the value of adding AS1402 to endocrine treatment and, if positive, will provide a firm basis for progress to a pivotal phase-III trial in breast cancer."