Journal of Clinical Oncology publishes IPI-504 Phase 2 study results

Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) announced that results from its Phase 2 study of IPI-504, a novel IV-administered Hsp90 chaperone inhibitor, in patients with advanced non-small cell lung cancer (NSCLC) were published in the Journal of Clinical Oncology (Sequist et. al., J Clin Oncol. doi: 10.1200/JCO.2010.30.8338, 2010). These data, presented previously at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO), documented for the first time the activity of an Hsp90 inhibitor in a molecularly defined cohort of patients with advanced NSCLC. In the study, IPI-504 was generally well tolerated and demonstrated clinical activity, particularly among patients with oncogenic anaplastic lymphoma kinase (ALK) gene rearrangements.

"These results support molecular analysis as a key tool in clinical trials to determine the signature of the best responding patients, and suggest that patients with NSCLC and ALK rearrangements may preferentially respond to Hsp90 chaperone inhibition," stated Lecia Sequist, M.D., MPH, from the Massachusetts General Hospital Cancer Center and an Assistant Professor of Medicine at Harvard Medical School. "We hope the ongoing study of IPI-504 in NSCLC patients with ALK rearrangements will validate these initial findings."

"We are encouraged that IPI-504 was generally well tolerated and demonstrated clinical activity in NSCLC, further supporting the clinical potential of Hsp90 chaperone inhibition as a targeted approach to treating certain cancers," stated Julian Adams, Ph.D., president of research and development, Infinity. "The results of the ongoing Phase 1b study of IPI-504 in combination with Taxotere^® in patients with solid tumors, as well as data from Dr. Sequist's study assessing IPI-504 in patients with NSCLC and ALK rearrangements, will help inform the path forward for IPI-504."

Trial Design and Results

The Phase 2 study of IPI-504 was designed to evaluate the safety, tolerability and anti-tumor activity of IPI-504 in patients with stage IIIb/IV NSCLC whose tumors had progressed after treatment with an EGFR tyrosine kinase inhibitor. Seventy-six patients were enrolled and stratified by their EGFR mutation status. A subset of patients also underwent EGFR (n = 25), KRAS (n = 30) and BRAF (n = 5) genotyping analysis, as well as a fluorescent in situ hybridization (FISH) assay to detect ALK gene rearrangements.

The results of the Phase 2 study show an objective response rate of seven percent in the overall study population: ten percent in patients who were EGFR wild-type, four percent in those with EGFR mutations, and 12 percent among KRAS wild-type patients. There was a 67 percent response rate among the patients with ALK rearrangements, with two of three patients experiencing partial responses and the third patient experiencing a 24 percent disease reduction. All three patients with ALK rearrangements received IPI-504 for at least six months.

IPI-504 was generally well-tolerated in this study. Most adverse events were Grade 1 or Grade 2. The most commonly reported adverse events (regardless of relationship to drug) were fatigue, nausea, diarrhea, vomiting and cough.

Source: Infinity Pharmaceuticals