Nektar Therapeutics has completed enrollment in the pivotal clinical study of etirinotecan pegol (NKTR-102) in patients with metastatic breast cancer. The phase III study, also known as the BEACON trial, is evaluating etirinotecan pegol versus a single-agent treatment of physician's choice for the treatment of locally recurrent or metastatic breast cancer.

Etirinotecan pegol is the first long-acting topoisomerase I inhibitor designed to concentrate in tumor tissue to provide sustained tumour suppression throughout the entire chemotherapy cycle.

"Strong interest in etirinotecan pegol and the BEACON study from investigators and patients has allowed us to rapidly complete our recruitment and enrollment," said Robert Medve, MD, senior vice president and chief medical officer of Nektar Therapeutics. "We recognise the high unmet need for new treatment options in the metastatic breast cancer setting, particularly among patients with HER2-negative breast cancer whose disease has progressed following anthracycline, taxane and capecitabine therapies. The primary endpoint in the BEACON study is survival and as we have previously announced, we plan to conduct an interim futility analysis for the BEACON study in the first quarter of next year with topline survival data to be available around the end of 2014."

Positive phase II data for etirinotecan pegol was previously announced and presented at the ASCO 2011 Breast Cancer Symposium (Garcia et. al., ASCO 2011). Etirinotecan pegol achieved a confirmed objective response rate by RECIST of 29 per cent. In addition, 71 per cent of patients in the study had no tumor progression, defined as complete response (CR), partial response (PR) and stable disease (SD), as measured by RECIST criteria. Etirinotecan pegol also demonstrated a high clinical benefit rate (CR+PR+SD greater than six months) of 46 per cent (30 of 66). Six patients experienced 100 per cent resolution of all target lesions, with two complete RECIST responses and four near-complete responses. Patients treated exhibited minimal alopecia, neuropathy and neutropenia, which are significant adverse events associated with existing breast cancer therapies. Side effects were generally manageable; the most common Grade 3 toxicity was diarrhoea (17-23 per cent) typically occurring after three months of therapy for both schedules.

BEACON is a phase III, open-label, randomized, multi-centre study of etirinotecan pegol in approximately 840 women with locally recurrent or metastatic breast cancer, who have previously been treated with anthracycline, taxane or capecitabine (ATC) treatments. The trial is being conducted at approximately 150 sites worldwide including North America, Eastern and Western Europe, and certain countries in Asia/Pacific. Patients were randomized on a 1:1 basis to receive 145 mg/m2 of single-agent etirinotecan pegol once every three weeks or a single agent of physician's choice. The physician's choice agents include: ixabepilone, vinorelbine, gemcitabine, eribulin, or a taxane. Randomization was stratified by geographic region, prior use of eribulin and receptor status.

The primary endpoint of the BEACON study is overall survival, and secondary endpoints include progression-free survival, objective tumour response rates (ORR), clinical benefit rate, duration of response, PK data, safety profiles, quality-of-life measurements, and pharmacoeconomic implications. The study is also evaluating specific biomarker data to assess correlation with objective tumor response rates, progression-free survival, overall survival and selected toxicities.

As a new long-acting topoisomerase I inhibitor, etirinotecan pegol has a non-overlapping mechanism of action with other agents used to treat breast cancer which may mitigate potential cancer cross-resistance and reduce overlapping toxicities. In November 2012, etirinotecan pegol was designated a Fast Track development program by the US FDA for the treatment of patients with locally recurrent or metastatic breast cancer progressing after treatment with an anthracycline, a taxane, and capecitabine (ATC).

Etirinotecan pegol is believed to penetrate the vasculature of the tumour environment more readily than normal vasculature, increasing the concentration of active drug within tumour tissue to enhance anti-tumor activity. In addition to metastatic breast cancer, etirinotecan pegol is also being evaluated for the treatment of ovarian, colorectal, glioma and non-small cell lung cancers.

Nektar Therapeutics is a biopharmaceutical company developing novel therapeutics based on its PEGylation and advanced polymer conjugation technology platforms.