A phase II trial of salirasib in patients with stage IIIB/IV lung adenocarcinoma enriched for KRAS mutations

8012 Background: KRAS mutations are present in 30% of lung adenocarcinomas and are associated with primary resistance to erlotinib and gefitinib. Salirasib severs RAS proteins from the membrane, decreasing function of all RAS isoforms. Salirasib inhibits KRAS-dependent growth in cell lines and xenograft models. This phase II study was designed to determine the activity of salirasib in patients (pts) with advanced NSCLC enriched for KRAS mutations. Methods: Two cohorts of pts with stage IIIB/IV NSCLC were eligible. Group A: pts with KRAS mutations previously treated with chemotherapy. Group B: previously-untreated pts with ≥15 pack-year smoking history. Salirasib was given orally, for days 1–28 of a 35 day cycle, with response assessment on day 28, day 63, and every 10 weeks (wks) thereafter. The primary endpoint was rate of RECIST non-progression at 10 wks. Secondary endpoints were response rate (RR), time to progression (TTP), overall survival (OS) and toxicity. Results: From August 2007-December 2008, 3...