Staff Writer

In an area that has seen several strike-outs recently, ArQule Inc. reported positive results in a midstage lung cancer trial, sending its shares soaring 63.4 percent Wednesday. Shares of ArQule (NASDAQ:ARQL) more than doubled in early trading Wednesday, before settling for a boost of $2.22, closing at $5.72.

Lead drug ARQ 197, when used with erlotinib (Tarceva), showed a 66 percent improvement in median progression-free survival (PFS) in patients with advanced, refractory non-small-cell lung cancer (NSCLC).

The median PFS was 16.1 weeks in the ARQ 197 plus erlotinib arm, compared with 9.7 weeks in the erlotinib plus placebo arm. But the difference between those two groups did not reach statistical significance when using a log-rank test.

However, the study did meet its secondary endpoint of median PFS in a subgroup of patients with nonsquamous histology, based on a Cox regression analysis. That group represented about 70 percent of patients enrolled in the trial, CEO Paolo Pucci said in a teleconference. He noted that the drug combination showed its greatest benefit in the group with non-squamous histology, where median PFS was 18.9 weeks in the treatment arm vs. 9.7 weeks in the control arm, which represents a 94 percent improvement.

"We believe the treatment benefit observed in this trial would represent a meaningful clinical improvement over standard therapy if replicated in Phase III trials," Brian Schwartz, chief medical officer of ArQule, said in a statement. "We are especially encouraged by the potential benefit for the large subgroup of nonsquamous cell patients."

ARQ 197 is an inhibitor of the c-Met receptor tyrosine kinase. Complete data from the lung cancer trial, which will include biomarker analyses, will be presented at a future medical meeting.

ArQule and partner Daiichi Sankyo Co. Ltd. have an agreement to co-develop and co-commercialize ARQ 197 in the U.S., Europe, South America and the rest of the world, excluding Japan, China (but including Hong Kong), South Korea and Taiwan, where Kyowa Hakko Kirin Co. Ltd. has exclusive rights for development and commercialization.

With so many setbacks lately in NSCLC, ArQule's study results were like a breath of fresh air for the Street.

The bad news in the lung cancer space continued this week when Antisoma plc and partner Novartis AG said they were stopping a Phase III trial of lead product ASA404 in NSCLC after an interim analysis showed the 1,200-patient study was futile. Novartis also is testing ASA404, a tumor vascular disrupting agent, as second-line treatment for NSCLC, and that 900-patient trial will continue to the interim analysis later this year. (See BioWorld Today, March 30, 2010.)

Two weeks ago Human Genome Sciences Inc. reported choppy results in a Phase II trial of mapatumumab (HGS-ETR1) in combination with paclitaxel and carboplatin as first-line therapy. While the regimen was well tolerated in the study, there was no difference in disease response or PFS between the mapatumumab-based regimen vs. the control group. The Rockville, Md.-based firm expects to present the results in full at a scientific meeting later this year. (See BioWorld Today, March 18, 2010.)

Also earlier this month, Seattle-based Oncothyreon Inc. said its partner, Merck Serono, had halted trials of Stimuvax in NSCLC after a study patient with multiple myeloma developed inflammation of the brain. As a result, Merck Serono, a unit of Merck KGaA and U.S. affiliate EMD Serono Inc., suspended further recruitment and ongoing treatment of patients in Phase III trials of Stimuvax (BLP25 liposome vaccine or L-BLP25) in NSCLC and breast cancer. (See BioWorld Today, March 24, 2010.)

In addition, Pfizer Inc. has discontinued a Phase III trial in first-line NSCLC due to lack of efficacy.

There have been other successes besides ArQule's. Abraxis BioScience Inc. appeared to squarely hit the mark in a Phase III lung cancer study. Abraxane combined with carboplatin was shown to be superior to Taxol plus carboplatin, in terms of overall response rate in a Phase III study in patients with NSCLC, according to Los Angeles-based Abraxis. (See BioWorld Today, March 18, 2010.)

Details of the Abraxane study were not disclosed, so there is no indication of how much of an improvement the Abraxane regimen was over the taxane-based treatment. The company plans to submit the data for consideration as a late-breaking presentation at the American Society of Clinical Oncology meeting in Chicago, June 4-8.

Abraxis is planning to file a supplemental new drug application in 2011 for Abraxane plus carboplatin as a first-line treatment for NSCLC.

On the horizon is Germany biotech Agennix AG's late-stage lung cancer drug candidate. The company recently raised about €9.8 million (US$13 million) in a private placement to fund its Phase III lung cancer trials. (See BioWorld Today, March 23, 2010.)

Agennix's FORTIS-M (monotherapy) study of talactoferrin is enrolling patients with NSCLC who have progressed on two or more therapies, and the FORTIS-C (combination) trial is evaluating talactoferrin plus carboplatin and paclitaxel in the first-line setting. Enrollment is expected to complete in the monotherapy lung cancer trial in the first half of 2011, and if the timelines hold, data could come at the end of that year.

In the third-line setting, the only product approved is Tarceva. In the first-line setting, several drugs such as Avastin and Alimta are approved for nonsquamous NSCLC only.