Armed with promising interim data from an ongoing Phase II study, Pharmion Corp. started a 480-patient pivotal trial of amrubicin, a third-generation anthracycline, in small-cell lung cancer.

The Boulder, Colo.-based firm said patient enrollment is under way, putting amrubicin only a few months behind development of its potential competitor, picoplatin, a platinum-based therapy from Poniard Pharmaceuticals Inc.

Both drugs are being tested as second-line SCLC treatments in patients with sensitive or refractory disease, and both will be evaluating overall survival as the primary endpoints, but Pharmion's Phase III study is using a "much more conventional approach" by testing amrubicin in a head-to-head comparison of chemotherapeutic agent topotecan, said Andrew Allen, Pharmion's executive vice president and chief medical officer.

South San Francisco-based Poniard, on the other hand, designed its Phase III study, designated SPEAR (Study of Picoplatin Efficacy After Relapse) to evaluate picoplatin plus best supportive care against best supportive care alone in 480 SCLC patients.

Poniard received a special protocol assessment in January and began the trial in May. If the study is successful, Poniard anticipates filing for approval in early 2009. (See BioWorld Today, Jan. 4, 2007.)

Pharmion's pivotal study will randomize patients in a 2-to-1 ratio to receive either amrubicin, delivered intravenously at 40 mg/m2 daily for three days, or 1.5 mg/m2 topotecan, given daily for five days. Both groups start on day one of a 21-day cycle. In addition to overall survival, the trial will measure secondary endpoints, including progression-free survival, overall response rate, duration of response and quality of life.

The company completed both an SPA with the FDA and the scientific advice process with the European Medicines Agency, so "our protocol has been exhaustively vetted by the regulatory authorities," Allen told BioWorld Today.

Patient enrollment is expected to take about 18 months, and since the trial is event-driven, it's difficult to predict an exact time frame, Allen said, though, since second-line median survival ranges from about five months to 11 months, he anticipates the study to take "about two to two and half years," putting potential regulatory filings in the 2010 to 2011 range, pending positive results.

One of the most aggressive cancer types, SCLC definitely is a disease in need of better drugs. Though topotecan (Hycamptin, GlaxoSmithKline plc) is considered the standard of care for SCLC, it's "not a very popular regimen" due, in part, to its toxicity, Allen said.

In sensitive SCLC patients, defined as those who responded to first-line platinum-based therapy and subsequently progressed 90 days or later after completing therapy, topotecan's median survival is about six to seven months.

"We're comfortably beating that in our Phase II program," he added, with interim data from 15 amrubicin-treated patients showing a 40 percent response rate, compared to no responses in the nine-patient topotecan-treated arm, and a median duration of progression-free survival of 4.1 months for the amrubicin vs. two months for patients receiving topotecan.

Pharmion is conducting a separate Phase II trial of amrubicin as a single-agent therapy in SCLC patients refractory to first-line therapy and another Phase II trial testing amrubicin as a single agent or in combination therapy with cisplatin vs. cisplatin plus etoposide in previously untreated extensive-stage patients.

"Next on the horizon, we'll be moving into first-line treatment," Allen said, adding that the European Organization for Research and Treatment of Cancer is conducting a Phase II trial in first-line SCLC.

Amrubicin previously gained approval in Japan, where it is marketed as Calsed for both SCLC and non-small-cell lung cancer by Tokyo-based Nippon Kayaku Co. Ltd. Pharmion picked up North American and European rights to the drug in its November 2006 buyout of San Diego-based Cabrellis Pharmaceuticals Inc. for $59 million. Under the terms of that deal, Pharmion will owe milestone payments of $12.5 million each upon amrubicin's approval in the U.S. and Europe, and would owe $10 million payments in each market if the drug reaches the market in a second indication. (See BioWorld Today, Nov. 17, 2006.)

Elsewhere in its pipeline, Pharmion is preparing to submit supplemental applications in the U.S. and Europe for Vidaza, its drug for myelodysplastic syndromes, to include the survival data reported in August.

The company also awaits survival data from the pivotal study of Orplatna (satraplatin), expected within the next month.

Though Pharmion, which has rights to satraplatin in Europe, submitted a marketing application based on positive progression-free survival data, its partner, GPC Biotech Inc., yanked its FDA application in July after an advisory panel recommended waiting for overall survival data before deciding on the drug's approval. (See BioWorld Today, July 25, 2007.)

Shares of Pharmion (NASDAQ:PHRM) closed at $48.74, up 37 cents.