7079 Background: Few prospective trials have been conducted in patients with advance thymic malignancies. Pemetrexed a multi-targeted antifolate with a broad range of clinical activity, but previously untested in thymic malignancies. As a result, a phase II trial was initiated to evaluate the clinical activity of pemetrexed in previously treated patients with thymoma (THY) and thymic carcinoma (TC). Methods: From February, 2005 to November, 2005, twenty-seven previously treated patients with unresectable stage IVA (n = 16) or stage IVB (n =11) disease were treated with pemetrexed at a dosage of 500 mg/m2 every three weeks for a maximum of 6 cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12 and steroid prophylaxis. Profile of patients include: median age = 52 years (range 26–84); M: F = 13:14; PS 0/1= 17/10; median number of prior therapies = 2 (range 1–6); 21 had prior radiation therapy; and histology (THY = 16, TC = 11). Results: The median number of cycles administered was 5 (range 1–6). Eleven patients had grade 3 toxicities including: dyspnea, infections, fatigue, abnormal chemistries and neutropenia. No Grade 4 toxicities were noted. Accrual was completed in November, 2005 with four patients still on therapy. In 23 fully evaluable patients, two complete and two partial responses (RECIST) were noted. All four responding patients had had stage IVA thymoma. Five patients progressed on therapy and two patients discontinued therapy for intolerance to chemotherapy (constipation, dyspnea) and 1 patient for progressive Morvan’s Syndrome. The median time to progression for all patients was 45 weeks (THY = 45.4 weeks vs. TC = 5.1 weeks). With three deaths thus far, the median overall survival has not been reached. Conclusions: Pemetrexed is an active agent in a heavily pretreated population of patients with recurrent thymoma. Patients with recurrent thymic carcinoma appear to have a much more aggressive clinical course than thymoma. [Table: see text]