Phase I and pharmacodynamic study of the histone deacetylase (HDAC) inhibitor romidepsin plus erlotinib in previously treated advanced non-small cell lung cancer (NSCLC).

8088^ Background: Preclinical studies have demonstrated anti-tumor efficacy of the combination of the HDAC inhibitor romidepsin plus erlotinib in NSCLC models insensitive to erlotinib monotherapy (eg, KRAS mutation, EGFR resistance mutation, EGFR wild type). Methods: This phase I study evaluated safety, pharmacodynamics, and preliminary activity of romidepsin (8-10 mg/m2) given IV days 1, 8, and 15 every 28 days plus erlotinib 150 mg PO daily in previously treated advanced NSCLC. In Cycle 1, erlotinib was initiated on Day 3, permitting pharmacodynamic analysis of romidepsin alone and in combination. Results: As of January 31, 2013, 15 patients (pts) have been treated: median age 60 years; 7 F, 8 M; all former or current smokers; 6 had prior erlotinib exposure; 8 adenocarcinoma, 6 squamous, 1 large cell; 5 EGFR wild type 1 KRAS mutation, 9 unknown mutation status. Most common related AEs regardless of grade were nausea (87%), vomiting (73%), fatigue (60%), diarrhea and rash (both 53%), and decreased appeti...