Synta Pharmaceuticals Corp. reported promising survival data from its successful Phase IIb study of its small molecule STA-4783 in metastatic melanoma as the American Society of Clinical Oncology meeting in Chicago came to an end Tuesday.

In an afternoon presentation, executives of the Lexington, Mass.-based company reported further analysis of its double-blind, randomized study of STA-4783 in combination with paclitaxel, which last fall hit its primary endpoint by doubling the progression-free survival compared to paclitaxel alone in patients with Stage IV disease. Further review showed that patients randomized to receive STA-4783 plus paclitaxel had a median survival of 12 months compared to 7.8 months for all patients who initially received paclitaxel alone.

If replicated in the company's upcoming Phase III study, expected to begin this summer, Synta President and CEO Safi Bahcall said that survival benefit "will be significant help in market penetration" for STA-4783, a product that has fast-track designation from the FDA. It adds to the "strong package of clinical data we have," he said during a company conference call Tuesday.

The trial randomized 81 patients on a 2-to-1 ration to receive either STA-4783 plus paclitaxel or paclitaxel alone. Patients in the chemotherapy-only group were allowed to cross over to the treatment group upon disease progression, and additional data showed that the median survival of the 19 patients who switched to the STA-4783 group had a median overall survival of 14.3 months. That compared to the median overall survival of 5.6 months for the nine patients who did not cross over. One year survival rates were 49 percent for patients in the STA-4783 group, 53 percent in the cross-over group and 22 percent for patients who did not receive STA-4783.

While some analysts on the call were concerned that the cross-over patients appeared to experience better survival than those treated with STA-4783 from the beginning of the trial, Bahcall said that figure included the paclitaxel-only treatment period prior to disease progression and trial investigator Steven O'Day called apparent disparity "background noise."

That might not have allayed investor fears, however. Synta's stock (NASDAQ:SNTA) dropped $1.19, or 11.7 percent, Tuesday to close at $8.96.

STA-4783's data compare favorably to results from other randomized trials in metastatic melanoma, which have shown median survival times of between six and nine months, regardless of treatment. Bahcall said the data stand out especially in an indication that historically has been hard to treat and "heightened by recent disappointments."

A number of drugs have fallen by the wayside in the melanoma space, and even a strong contender like Nexavar (sorafenib, from partners Onyx Pharmaceuticals Inc. and Bayer Pharmaceuticals Corp.), which is approved in kidney cancer and reported positive liver cancer data at ASCO earlier this week, failed to show significant improvement in that indication. The drug missed its endpoint in a Phase III melanoma trial in December. (See BioWorld Today, Dec. 5, 2006.)

Armed with the Phase IIb data, Synta is gearing up to begin a pivotal Phase III trial, expected to follow a similar design as the Phase II study, with progression-free survival as the primary endpoint. The company anticipates final data from the study by the end of 2008.

Synta also "intends to explore [STA-4783] in additional indications," Bahcall said, and anticipates starting one or more Phase II studies later in the year.