7030 Background: Amatuximab (MORAb-009) is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in many cancers including malignant mesothelioma (MM). Based on safety of amatuximab in phase I clinical trial and pre-clinical studies showing synergy in combination with chemotherapy, a single arm phase II study of amatuximab plus pemetrexed (P) and cisplatin (C) was initiated in pts. with MM. Methods: Eligibility criteria included pts. with unresectable epithelial or biphasic pleural MM, no prior chemotherapy and KPS > 70%. Pts. received amatuximab 5 mg/kg on days 1 and 8 with P 500 mg/m2 and C 75 mg/m2 (PC) given on day 1, of each 21 day cycle for 6 cycles. Pts. with objective response or stable disease received amatuximab monotherapy until disease progression. Primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were overall survival (OS), objective response rate and safety of amatuximab with PC. Results: From 2/2009 to 10/2010, 89 pts. were enrolled at 26 sites. Pt. characteristics: median age 67 yrs. (range 46-80), 78% male, 70% with KPS >90%, 89% epithelial MM, 11% biphasic MM and 88% had stage III/IV disease. Median number of PC plus amatuximab cycles was 5 (range 1-6) and 56 (63%) pts. received single agent amatuximab. In addition to the expected toxicity from PC, hypersensitivity reactions (12.4%; Grade 3/4=4.5%) from amatuximab were noted. By independent radiological review 30 (39%) pts. had partial response and 39 (51%) had stable disease. PFS at 6 months was 52% (95% CI: 39.5-63.5) with a median PFS of 6.1 months (95% CI: 5.4-6.5). As of 1/10/12 the median OS was 14.5 months (95% CI: 12.4-18.5) with 31 pts. still alive and 7 pts. receiving maintenance amatuximab. Conclusions: Amatuximab in combination with PC was generally well-tolerated in this study with 90% of pts. having an objective tumor response or stable disease by independent radiological review. Although PFS is not significantly different from historical results of PC alone, the median OS is 14.5 months with 35% of pts. still alive. Updated OS and biomarker data will be presented at the meeting.