Background: AT-101 (AT) is an oral BH3 mimetic that lowers the apoptotic threshold by inhibiting heterodimerization of Bcl-2, Bcl-xL, Mcl-1 and Bcl-W, up-regulating pro-apoptotic proteins noxa and puma and inhibiting angiogenesis. Synergistic anti-tumor activity as been observed in vitro with EP in combination with agents that suppress Bcl-2 expression. This study was conducted to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic (PK) profile and preliminary anti-tumor activity of AT and EP. Methods: Adult pts with relapsed or refractory advanced solid tumors received AT orally BID days (D) 1-3, P IV D 1, and E IV D 1-3 of a 21-D cycle. We previously reported the MTD without pegfilgrastim (F) was AT 20 mg BID , P 60 mg/m², and E 100 mg/m² (Leal, JCO 2009; 27(15S), e13502). Pts were enrolled in 3 additional dose levels (DL) with F support (6 mg SQ day 4): DL1a (AT 30 mg, P 60 mg/m², and E 100 mg/m²), DL2a (AT 30 mg, P 60 mg/m², and E 120 mg/m²), and DL3a (AT 40 mg, P 60 mg/m², and E 120 mg/m²). Results: 12 additional pts were enrolled: 8 men, 4 women. Tumor types: 4 non-small cell lung cancer (NSCLC), 1 ES-SCLC, 2 esophageal, 2 high-grade (HG) neuroendocrine, 1 prostate, 1 adrenocortical, 1 gallbladder. No dose limiting toxicities occurred. Grade 3/4 treatment-related toxicities included: 2 pts with diarrhea (1 at DL1a and 1 at DL3a), and 1 episode, each, of increased ALT (DL1a), hypokalemia (DL1a), fatigue (DL2a), neutropenia (DL2a), anemia (DL3a), hypophosphatemia (DL3a), and pulmonary embolism (DL3a). Dose-proportional PK was observed with a mean AT t_1/2 of 3.32 hr (range 2.86-3.94). No PK interactions were observed between the agents. Two pts with NSCLC and 1 with HG neuroendocrine tumor had a PR. Conclusions: The MTD with F was established at AT 40 mg BID D1-3, P 60 mg/m² D1, and E 120 mg/m² D1 of a 21 D cycle. F support permitted standard doses of EP without dose limiting neutropenia. Anti-tumor activity was observed in NSCLC and HG neuroendocrine tumor. Accrual to an MTD expansion cohort of pts with untreated ES-SCLC is ongoing. This study was supported by NCI UO1 CA062491, SAIC 25XS097, and 1ULRR025011.