610 Loss of the Tumor Suppressor Merlin as a Potential Predictive Biomarker of Clinical Activity for the Oral, Focal Adhesion Kinase (FAK) Inhibitor GSK2256098 in Pts with Recurrent Mesothelioma

Results: Preliminary data are presented for 43 patients (25 M, 18 F), median age 64 years. No dose-limiting toxicities or serious toxicity patterns occurred at any dose level. Drug-related adverse events occurring in 10% of patients were fatigue (28%), decreased appetite (23%), nausea (16%), diarrhea (14%), and anemia (12%); the majority were grade 2. Perturbations in insulin and growth hormone were not observed. Clinically significant changes in serum glucose were rare. The MTD was not reached after completely enrolling patients through the highest dose, 45mg/kg IV q3w. Serum exposure of MEDI-573 increased with increasing dose. Full suppression of IGF-I/-II was achieved with weekly and q3w dosing. No neutralizing antibodies against MEDI-573 were detected. Of 43 patients, 13 (30%) had stable disease with 8 (19%) of 12 weeks duration. The longest exposure was 21 months in a patient with well-differentiated liposarcoma. Conclusions: MEDI-573 demonstrated an acceptable safety profile at all doses tested. No dose-limiting toxicity or serious toxicities, including those related to glucose homeostasis, were detected. These preliminary results support further clinical development. This study was funded by MedImmune, LLC.