7071 Background: Ras activation (mutational or non-mutational) is a key pathway for survival and proliferative advantage of leukemic cells. Farnesyl transferase inhibitors (FTI) that are thought to alter lipid modification of Ras and thereby alter its membrane targeting, are in clinical trial in hematologic malignancies but their target may not be specific for Ras. Toxicities of FTIs include diarrhea, skin rash and hepatic toxicity. FTS is an oral Ras inhibitor that causes dislocation of Ras from its membrane location by competing directly with farnesylated Ras to bind to its putative membrane binding proteins. FTS does not inhibit farnesyl transferase enzyme. Methods: We report on an ongoing phase I study of FTS in patients with relapsed/refractory hematologic malignancies in which FTS is administered orally twice daily on days 1–21 of a 28 day cycle in a “3+3” dose escalation design. Results: To date, 12 patients (pts) have been enrolled, with 11 pts treated (1 cycle=3, 2 cycles=5, 4cycles=1, 2= too early). Four pts were enrolled at dose level (DL) of 100 mg , 3 pts at each DL of 200 and 400 mg and 2 pts at DL of 600 mg. One pt enrolled at 100 mg DL was never treated. Median age was 74 years (range, 57 to 85 years), median ECOG status 1 (range, 0–2) and median no. of prior therapies 2 (range, 0–7). Diagnoses included: Acute myelogenous leukemia (AML) = 6 pts, myelodysplastic syndrome (MDS) = 4 pts, chronic myelomonocytic leukemia (CMML) = 1 pt and chronic myelogenous leukemia (CML) = 1 pt. Of 9 pts evaluable for response, 6 pts (3 MDS, 1 CMML, 2 AML) had hematological improvement (HI) (3 in two lineages, 3 in one lineage). Grade 1 diarrhea has been the only non-hematologic toxicity seen, observed in 8 of 10 (80%) pts evaluable for toxicity and is completely correctable with oral antidiarrheals. Conclusions: FTS shows promising activity in refractory hematologic malignancies and to date has minimal toxicity. No significant financial relationships to disclose.