Good survival results in phase II study of ASA404 in NSCLC

SEOUL, South Korea—A phase II study of Antisoma's investigational agent ASA404 in combination with carboplatin and paclitaxel showed positive survival results in non-small-cell lung cancer patients. Mark McKeage, MD, of the University of Auckland, New Zealand, presented the data for the ASA404-201 Study Group at a poster session of the 12th World Conference on Lung Cancer.

ASA404 is a small-molecule vascular disrupting agent. It attacks existing tumor blood vessels selectively, causing rapid shutdown of tumor blood flow, Dr. McKeage said.

Median survival 14.9 months

The single-arm trial, which used an 1,800 mg/m² dose of ASA404, found median survival of 14.9 months, median time to tumor progression of 5.5 months, and tumor response rate of 37.9%. The addition of ASA404 to chemotherapy was well tolerated, and safety findings were similar in patients with squamous and nonsquamous lung cancer.

The trial was an extension of an earlier randomized phase II trial in which the addition of ASA404 to chemotherapy produced one of the largest increases in median survival ever reported in advanced lung cancer, Antisoma said in a press release.

In that trial, patients who received a 1,200 mg/m² dose of ASA404 combined with chemotherapy had a median survival of 14.0 months vs 8.8 months for chemotherapy alone. Response rates were 31.2% with ASA404 vs 22.2% with chemotherapy alone. Time to tumor progression was 5.4 months vs 4.4 months, respectively.

"This is a second set of positive data on ASA404 in lung cancer," Dr. McKeage said. "It is particularly encouraging to see more evidence that patients receiving ASA404 on top of chemotherapy may live longer than we would expect with chemotherapy alone."

Glyn Edwards, Antisoma's CEO, said: "These data add considerably to the strength of the evidence supporting ASA404 in its lead indication and give us extra confidence as the drug proceeds into phase III testing."

Evaluating a higher dose

The aim of the current study was to evaluate a higher dose of ASA404 than used in other phase II trials of the agent. As in the earlier randomized study, patients received first-line chemotherapy for stage IIIb or IV NSCLC. A total of 32 patients were enrolled at hospitals in Germany, Australia, and New Zealand; 31 were eligible and 30 actually received ASA404.

Adverse events

The most commonly reported serious adverse events were neutropenia and peripheral neuropathy. The incidence of neutropenia was higher than expected for standard chemotherapy alone. There were no serious cardiac adverse events, and the addition of ASA404 to standard chemotherapy was not associated with clinically significant ophthalmic abnormalities.

"The 1,800 mg/m² dose, a 50% higher dose than used in previous phase II studies, is a viable dose for future combination studies," Dr. McKeage said.

Novartis, Antisoma's partner in the development of ASA404, plans to start enrolling NSCLC patients into a phase III trial in early 2008.