Antisoma Starts Phase II Trial Of AS1402 In Breast Cancer

Main Category: Breast Cancer
Also Included In: Cancer / Oncology;  Women's Health / Gynecology;  Clinical Trials / Drug Trials
Article Date: 30 Sep 2008 - 5:00 PDT

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Cancer drug developer Antisoma plc (LSE: ASM; USOTC: ATSMY) announced that it 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% 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 MD 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."

Background on the AS1402 phase II trial

Additional details of the phase II trial of AS1402 will be available shortly at http://www.clinicaltrials.gov. In this study, the anti-MUC1 antibody AS1402 is being tested in combination with a widely used endocrine (hormonal) therapy, letrozole, which belongs to the class of aromatase inhibitors. This is the first study to evaluate AS1402 as part of a combination regimen, phase I trials having tested AS1402 as a single agent. It is believed to be the first trial to combine a MUC1-targeting antibody with endocrine treatment for cancer. Endpoints in the phase II trial include response rates, time to tumour progression, progression-free survival and clinical benefit rate (sum of patients showing a response or disease stabilisation by 'RECIST' (Response Evaluation Criteria In Solid Tumours)).

Background on AS1402

AS1402 (huHMFG1, previously known also as R1550 and Therex) is a humanised antibody against a form of MUC1 found on the surface of various cancers. The drug has successfully completed phase I studies in breast cancer. It was licensed by Antisoma from the Imperial Cancer Research Technologies, the technology transfer arm of the Imperial Cancer Research Fund (now Cancer Research UK).

AS1402 is a humanised antibody that attacks cancer cells by recruiting the patient's immune system, particularly natural killer cells. This is the process of antibody-dependent cellular cytotoxicity (ADCC), which has been demonstrated during experiments in vitro with the AS1402 antibody. A growing body of evidence links the MUC1 protein targeted by AS1402 with cancer progression and metastasis. In particular, MUC1 has been implicated in changes in intracellular signalling and altered interactions with extracellular matrix components such as ICAM-1. These findings reinforce the relevance of MUC1 as a target for anti-cancer treatments and open up the possibility that, in addition to mediating ADCC, naked anti-MUC1 antibodies such as AS1402 may exert effects on cancer cells by altering the interactions of MUC1 with other proteins.

Background on Antisoma

Antisoma is a London Stock Exchange-listed biopharmaceutical company that develops novel products for the treatment of cancer. The Company has operations in the UK and the US. Please visit http://www.antisoma.com for further information about Antisoma.

Antisoma Plc