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A pivotal phase III study is currently underway to evaluate the efficacy and safety of Novartis’ novel anti-cancer compound ASA404 in patients with non–small cell lung cancer (NSCLC). NSCLC is the most prevalent cause of cancer death among men and women in the United States and globally.
In April 2008, Novartis investigators, in conjunction with various academic partners, began enrolling patients with NSCLC in phase III of the ongoing ATTRACT-1 (Anti-vascular Targeted Therapy: Researching ASA404 in Cancer Treatment) trial. This randomized double-blind placebo-controlled multicenter study includes 1200 patients from more than 200 sites in 20 countries.
The study comes on the heels of successful phase I and II research, which yielded strong evidence of promising patient outcomes with ASA404 treatment. In the earlier randomized phase II study, a combination of ASA404 and chemotherapy as first-line treatment of advanced NSCLC demonstrated a median overall survival advantage of more than 5 months compared with chemotherapy alone. Researchers observed a similar survival advantage in a subsequent extension of the phase II study.
The phase III trial will evaluate the efficacy of ASA404 in combination with paclitaxel (Taxol) plus carboplatin as first-line treatment for locally advanced or metastatic (stage IIIB/IV) NSCLC of squamous or nonsquamous histology. Patients will be randomly assigned at a ratio of 1:1 to receive either ASA404 1800 mg/m2 or placebo in combination with a chemotherapy regimen of carboplatin plus paclitaxel. Treatment will continue for up to six 21-day cycles (126 days total) over 4.2 months.
ASA404 is a tumor-vascular disrupting agent that selectively causes the collapse of a tumor’s existing blood supply, leading to extensive tumor cell death (apoptosis). According to a Novartis spokesperson, ASA404 has a novel mechanism of action that may represent a new approach to treating NSCLC. For example, the action of ASA404 is distinct from that of angiogenesis inhibitors, which inhibit the formation of new tumor blood vessels rather than disrupting existing blood supply to tumors.
Commenting on company expectations for the ATTRACT-1 trial, Alessandro Riva, executive vice president and global head of development, Novartis Oncology, said, “With the launch of ATTRACT-1, we look forward to exploring the unique mechanism of action of ASA404 in NSCLC to potentially help the more than 1 million people who develop lung cancer each year.”
David Epstein, president and CEO, Novartis Oncology, added, “Today, our broad and deep pipeline includes both small molecules and monoclonal antibodies that utilize a variety of mechanisms, such as vascular-disruption, anti-angiogenesis, and kinase inhibition, to treat cancer. These exciting potential discoveries have the possibility to change medical treatment for patients suffering with many forms of cancer.”
Novartis signed an exclusive licensing agreement with Antisoma plc, London, for the worldwide rights to ASA404 in April 2007, and it is 1 of 6 prospective oncology compounds Novartis is developing for potential registration over the next 5 years. Novartis’ other investigational therapies, which focus on a broad array of cancer targets, include RAD001, a treatment for renal cell carcinoma and other cancers; SOM230 to treat Cushing’s disease, refractory carcinoid tumors, and acromegaly; LBH589 for cutaneous T-cell lymphoma, as well as other cancers; EPO906 to treat ovarian cancer; and PKC412, a treatment for acute myelogenous leukemia and aggressive systemic mastocytosis.