Open-Label Phase Ib Study Of Entinostat (E), And Lapatinib (L) Alone, And In Combination With Trastuzumab (T) In Patients (Pts) With Her2+Metastatic (Mher2+) Breast Cancer After Progression On Trastuzumab.

609Background: Entinostat (E) an HDAC inhibitor, and Lapatinib (L) given in combination induces FOXO3a and mediates Bim1 expression in HER2+ cell lines resulting in apoptosis [Lee et al. BCRT 2014], providing rationale for this NCI/CTEP sponsored phase 1b trial of E and L +/- T in mHER2+ breast cancer. Methods: A 3+3 phase 1b design was used to determine MTD. Group 1 received E and L. Group 2 received E, L and T. MTD was E 15mg q 2 wks, L 1250mg q 28 days (Group 1), E 12mg q 2 wks, L 1000 mg q 28 days and T 8mg/kg -u003e 6mg/kg q 3 wks (Group 2); 11 pts received E, L and T at MTD in an expansion cohort. Results: 37 pts were enrolled (15 Group 1, 11 Group 2, and 11 dose expansion); 18 had evaluable circulating tumor cells (isolated using ApoCell’s ApoStream technology) with Akt, HER2, EGFR for further correlative analysis. Median age was 52 (26-72 yo), received 3 (1-15 lines) previous therapies; 13 pts in Group 1, and 19 pts in Group 2/expansion had evaluable response to date. Total 9(24%) pts had clinical ben...