Phase I Study of Temsirolimus in Combination with Cetuximab in Patients with Advanced Solid Tumors.

2599 Background: Preclinical studies suggest that temsirolimus (T), an inhibitor of mammalian target of rapamycin (mTOR) combined with cetuximab (C), an anti-EGFR monoclonal antibody, may have synergistic antitumor effects. Methods: A dose escalation study was conducted to define the MTD and to characterize the pharmacokinetics and safety profile of T (30 min infusion) given 1 hour later after C (1 hour infusion) on a weekly schedule of a 28-day cycle. Five dose-levels were evaluated with dose range of T from 15 to 25 mg weekly and C from 150 to 250 mg/m2weekly. Sequential biopsies were mandatory during the expansion cohort. Results: 39 patients (15M/24F), median age 57 years (range 38-76), previous number of lines 3 (range: 2-15) received the combination of T + C. The most common tumor types were colorectal (N = 6), breast (N = 5), uterine cervix SCC (N = 4) and NSCLC (N = 4). Three patients experienced dose limiting toxicities: grade 3 pulmonary embolism (at C 200 + T 20 level), grade 3 stomatitis (at C...