ARQ 197 demonstrates 66% improvement in median PFS in patients with advanced NSCLC

ArQule, Inc. (Nasdaq: ARQL) today announced that ARQ 197, when used in combination with erlotinib, demonstrated a 66% improvement in median Progression-Free Survival (PFS) in patients with advanced, refractory non-small cell lung cancer (NSCLC). In the intent to treat (ITT) population (n = 167), median PFS was 16.1 weeks in the ARQ 197 plus erlotinib arm, compared with 9.7 weeks in the erlotinib plus placebo arm.

“We are especially encouraged by the potential benefit for the large sub-group of non-squamous cell patients. We will thoroughly analyze our extensive database from this trial, including additional patient sub-group characteristics, to optimize ongoing and future trials of ARQ 197.”

The difference in PFS between the two arms did not achieve statistical significance (hazard ratio = 0.809) by applying a log-rank test. When adjusting for imbalances in the distribution of key prognostic factors, the difference in PFS was statistically significant (hazard ratio = 0.675) by applying a Cox regression analysis specified for secondary efficacy analyses.

Improvement in median PFS was more pronounced in the pre-defined sub-group of patients with non-squamous histology (n = 117); median PFS was 18.9 weeks in the treatment arm versus 9.7 weeks in the control arm, which represents a 94% improvement. Based on an exploratory Cox regression analysis, the endpoint of PFS was met in the sub-group and achieved statistical significance (hazard ratio = 0.613).

There were no clinically relevant differences in adverse event rates between the treatment and control arms. The majority of adverse events were mild in intensity and included rash, diarrhea and fatigue.

"We believe the treatment benefit observed in this trial would represent a meaningful clinical improvement over standard therapy if replicated in Phase 3 trials," said Dr. Brian Schwartz, chief medical officer of ArQule. "We are especially encouraged by the potential benefit for the large sub-group of non-squamous cell patients. We will thoroughly analyze our extensive database from this trial, including additional patient sub-group characteristics, to optimize ongoing and future trials of ARQ 197."

Complete data from this trial, which will include biomarker analyses, will be presented at a future medical meeting during 2010.

One hundred sixty-seven patients were evaluated in the Phase 2 trial. Participating patients were EGFR (epidermal growth factor receptor) inhibitor naïve and were randomized one-to-one to receive either the combination of ARQ 197 plus erlotinib or placebo plus erlotinib in second and third line settings. ARQ 197 is an orally available, small molecule inhibitor of the c-Met receptor tyrosine kinase. Erlotinib, marketed as Tarceva™, is an inhibitor of the EGFR tyrosine kinase.

ARQ 197 is also currently being evaluated in clinical trials as a single agent and in combination with other anti-cancer therapies in a number of indications, including c-Met-associated soft-tissue sarcomas, hepatocellular carcinoma, pancreatic adenocarcinoma, germ cell tumors and colorectal cancer.

Patients, physicians and other healthcare professionals seeking additional information regarding trials involving ARQ 197 may call 1-800-373-7827.

The American Cancer Society's estimates of the impact of lung cancer in the U.S. during 2009 include approximately 219,000 new cases (both non-small cell and small cell) and 159,000 deaths resulting from the disease, accounting for 28 percent of all cancer deaths. Lung cancer is the leading cause of cancer death among both men and women.