Nektar Therapeutics has announced that the Independent Data Monitoring Committee (DMC) created to provide safety oversight for the company's pivotal clinical study for etirinotecan pegol (NKTR-102) has recommended continuation of the BEACON phase III trial, based upon the completion of a planned interim efficacy analysis in accordance with the DMC charter. The BEACON trial is evaluating NKTR-102 versus an agent of physician's choice for the treatment of locally recurrent or metastatic breast cancer, with a primary efficacy endpoint of overall survival. NKTR-102 is the first long-acting topoisomerase I-inhibitor designed to concentrate in tumor tissue, provide sustained tumor suppression throughout the entire chemotherapy cycle and to reduce the peak exposures that are associated with toxicities of other cytotoxics.
The independent DMC performed the pre-defined interim efficacy analysis, which consisted of a review of ongoing efficacy and safety data, including 50% of patient events necessary to evaluate the primary endpoint of overall survival. In August 2013, the BEACON study completed enrollment of 852 patients with advanced breast cancer whose disease has progressed following treatment with anthracycline, taxane and capecitabine therapies (ATC).
"While the results of BEACON remain blinded to Nektar, we are very pleased that the NKTR-102 trial has successfully passed this important interim efficacy analysis," said Howard Robin, president and CEO of Nektar Therapeutics. "We expect final results from the study at the end of 2014 or early 2015, and if positive, we plan to submit filings in the U.S. and Europe in the second half of 2015. There is a high unmet need for new treatment options for patients with advanced breast cancer, particularly for patients with HER2-negative breast cancer and triple-negative breast cancer."
Positive phase II data for NKTR-102 were recently published in Lancet Oncology in November. Etirinotecan pegol achieved a confirmed objective response rate by RECIST of 29%. NKTR-102 demonstrated a high clinical benefit rate (CR+PR+SD greater than six months) of 37% (13/35) in the 14-day group and 49% (17/35) in the 21-day group. Six patients experienced 100% resolution of all target lesions, with two complete RECIST responses and four near-complete responses. Patients treated exhibited low rates of 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 diarrhea (17-23%) typically occurring after three months of therapy.
BEACON is a phase III, open-label, randomized, multicenter study of NKTR-102 which enrolled 852 women with locally recurrent or metastatic breast cancer, who have previously been treated with ATC. The trial is being conducted at approximately 150 sites worldwide including North America, Western Europe, Russia and the Republic of Korea. Nearly half of the patients enrolled in BEACON were located in North America. Patients were randomized on a 1:1 basis to receive 145mg/m2 of single-agent NKTR-102 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; secondary endpoints include progression-free survival, objective tumor response rates (ORR), clinical benefit rate, duration of response, pharmacokinetics, safety, quality-of-life measurements and pharmacoeconomic implications. The study also is evaluating specific biomarker data to assess correlation with objective tumor response rates, progression-free survival, overall survival and selected toxicities.
NKTR-102 is a new therapeutic option in development for advanced breast cancer. It is the first long-acting topoisomerase I inhibitor with 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, NKTR-102 was designated a Fast Track development program by the FDA for the treatment of patients with locally recurrent or metastatic breast cancer progressing after treatment with ATC.
NKTR-102 is believed to penetrate the vasculature of the tumor environment more readily than normal vasculature, increasing the concentration of active drug within tumor tissue to enhance anti-tumor activity. The unique PK profile of NKTR-102 provides continuous exposure of active drug throughout the entire chemotherapy cycle, with reduced peak exposures that can be associated with toxicities. In addition to metastatic breast cancer, NKTR-102 also is being evaluated for the treatment of ovarian, colorectal, glioma and lung cancers.