4587 Background: We report on MCC preclinical activity and the results from 2 clinical trials in patients with carcinoma in situ of the bladder (CIS). Methods: Immune stimulatory and anti-cancer activities of MCC were determined; toxicology profile following intravesical and intravenous administration was characterized. Clinical efficacy and safety were evaluated in two trials where 128 patients with CIS associated or not with papillary tumors (<T2) received MCC (4 or 8 mg). Patients received 6 weekly intravesical instillations and a maintenance treatment of up to 10 months. Safety was evaluated by adverse events (AEs); complete response (CR) was defined as negative biopsy, cystoscopy and cytology. Results: Apoptosis and inhibition of proliferation were shown in vitro in bladder cancer ATCC cell lines and in human bladder tumour cells in primary culture. Immuno-stimulation was seen in human PBMC. In toxicology studies MCC was non toxic intravenously at a human equivalent dose up to 4.32 mg/kg. In 2 clinical studies MCC was well tolerated by all patients with 20–37% drug related AEs and less than 1% drug-related SAEs. The CR rates were 63%, 49% and 41% at weeks 12, 24 and 60 for the phase I study. For the phase II study, the CR rates at weeks 12, 26, months 12 and 18 in the ITT population were 27%, 27%, 32% and 23% at a dose of 4 mg and 46%, 46%, 64% and 73% at a dose of 8 mg. Increases in urinary cytokines and apoptosis markers were observed in the majority of patients. Conclusions: Pre-clinical and clinical data demonstrated anticancer activity of MCC, clinical efficacy and an excellent safety profile. MCC is different from and has a different mechanism of action than BCG, the standard treatment for CIS. A multicenter phase 3 trial is being set up to confirm the efficacy and safety of MCC at a dose of 8 mg. No significant financial relationships to disclose.