Background: MT110 is a bispecific T cell engaging antibody construct (BiTE) that directs CD3 expressing T cells to kill target cells that express EpCAM, which is widely found on solid tumors. Methods: Safety, tolerability, pharmacokinetics and anti-tumor activity of MT110 in patients (pts) with advanced solid tumors were studied using a 3+3 design. Continuous IV infusions for at least 28 days of doses ranging from 1 to 48 µg/d have been tested. Stepwise intra-patient dose escalations within cycle 1 or at start of cycle 2 have been explored. Results: 51 pts (6 gastric cancers, 32 CRC, 2 SCLC, 5 NSCLC, 3 HRPC, 1 ovarian cancer) have been treated in 12 dose cohorts. The maximally administered dose includes day 1 dose of 3 µg/d escalated up to 48 µg/d. The maximum tolerable dose (MTD) has not yet been established. Diarrhea and elevations in liver function tests have been reported as dose limiting toxicity (DLT) for individual patients. Transaminase elevations were fully reversible and mitigated by dexamethasone at initiation or escalation of dose. Other adverse events of grade 3 or higher included transient lymphopenia, increase in lipase or amylase, nausea, vomiting, and hypoalbuminaemia. No CNS safety signal was observed. The mean serum half-life of MT110 was 4.5 hours. Mean steady state serum concentrations of MT110 were linear with dose across treatment cycles. At 48 µg/d, the mean Css was 3.2 ng/mL. This compares to preclinical EC90 of 1.35 – 3.85 ng/ml in CRC cell lines. Sixteen pts who received a dose of ≥ 24 µg/d were evaluable for anti-tumor response. Best response of SD was reported in 38%; median duration was 155 days (95% CI 92; 161). Anti-tumor activity was demonstrated on biopsy of liver metastases in one patient. Following at least 1 week of MT110 treatment at 48 µg/d, a decrease in circulating tumor cells was observed with a median nadir 74% below baseline. Conclusions: The use of stepwise dose escalation and concomitant dexamethasone resulted in improved tolerability. A dose of 48 µg/d appears tolerable. Tumor biopsy evaluation on treatment and pharmacodynamic evidence of anti-tumor activity are encouraging. Additional dose cohorts will seek to identify the recommended phase II dose and further evidence of anti-tumor activity.