Wan-Teck Lim, Guek Eng Lee, Noan Minh Chau, Mei-Kim Ang, Eng Huat Tan, Balram Chowbay, Daniel Shao-Weng Tan, Dawn Q. Chong, Thuan Tong Tan, Quan Sing Ng, John E. Connolly, and Liz Zhong
3098 Background: Histone deacetylase and mTOR inhibition circumvent critical EBV-oncogenic pathways with preclinical studies demonstrating lytic induction in EBV infected cells, as well as immunomodulatory and antiangiogenic effects. Methods: Patients (Pt) with advanced solid tumors enriched for EBV–related cancers were enrolled to determine safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics and preliminary antitumor activity. LBH was instituted 7-days prior to combination treatment. NPC pt received antiviral prophylaxis of either acyclovir (Ac) or valaciclovir (Vc). Serum EBV DNA levels (EBNA-1) were measured weekly and plasma cytokines profiled using a 31-plex Luminex panel. Results: 15 pt have been treated (M:F 13:2, median age 50, R: 38-63) 10 NPC, 5 non-NPC (colon, RCC, breast, gastric, sarcoma) at 3 dose levels – LBH (3x/wk)-EVE (daily):10-2.5, 10-5, 15-5. Two dose limiting toxicities of G4 (grade) thrombocytopenia were observed at LBH15-RAD5. Significant adverse events (AE) (G≥3) were dysphagia (1) and thrombocytopenia (3). Common AEs (G1/2) included fatigue (80%), anorexia (60%), mucositis (53%), xerostomia (26%), dysphagia (26%). Two minor responses were seen (1 NPC, 1 breast) and 2 pt (1 NPC, 1 RCC) had prolonged stable disease (>16 weeks). Modulation of EBV DNA titres was seen only in NPC pt, with median fold-change from baseline of 10.9 (0.05-174). Pt on Ac prophylaxis (n=5) had significant increases in DNA titres (9-174 fold), while those on Vc (n=4) were less pronounced (0.05-11 fold, p