A phase I dose escalation study of the tolerability of the oral VEGFR and EGFR inhibitor vandetanib (V) in combination with the oral MEK inhibitor selumetinib (S) in solid tumors.

2583 Background: The clinical utility of agents that target EGFR and VEGFR signaling in Non-Small Cell Lung Cancer (NSCLC) is limited by resistance due to emergent alternative growth stimulatory pathways, particularly that of MEK. Thus, there is a strong rationale for developing a strategy to combine EGFR, VEGFR and MEK inhibitors. Methods: Patients (Pts) aged > 18y, life expectancy > 12w and cytologically proven solid tumors for which no conventional therapy exists were eligible to participate. Six dose levels have been explored. PK samples were obtained on D4, 15 and 29. Pts remained on treatment until progressive disease or unacceptable toxicity. Results: 41 pts of median age 62y (36 – 80y); M-20, F-21; lung-23, CRC-9, Mesothelioma-3, pancreas-2, Other-4 were enrolled. 40 pts were eligible for safety assessment. Median treatment time was 10 w (range 2-44 w). GI and skin toxicities were the most prevalent related AEs (GI: 124 AEs in 88% pts; Skin: 74 AEs in 95% pts). Sixteen related eye disorders were s...