Results of a phase 1 clinical trial investigating a combination of the oral mTOR-inhibitor Everolimus (E, RAD001) and Gemcitabine (GEM) in patients (pts) with advanced cancers

3120 Background: Pre-clinical studies of E have shown dose-dependent inhibition of tumor growth, reduced tumor vascularity and potentiation of the activity of a number of cytotoxics, particularly GEM. This phase 1 study investigated E alone and then in combination with GEM. Initially, pts with advanced, refractory solid tumors were recruited to a dose-escalation study with E given weekly to investigate safety, pharmacokinetics (PK) and optimal biological dose (OBD) as shown by sustained inhibition of the mTOR downstream substrate, S6 kinase 1 in peripheral blood mononuclear cells, comparable to that associated with anti-tumor activity in preclinical models. The OBD was concluded to be 20mg and was well tolerated. Methods: In a new cohort, the OBD was combined with GEM 600mg/m2 given IV, weekly, for 3 weeks in 4-week cycles. Sequential cohorts were planned with incremental doses of 800, and 1,000 mg/m2 to identify the maximum tolerated dose. Results: 8 pts were recruited to an expanded first dose level for...