4163 Background: Preclinical studies have implicated the IGF-1 receptor in the progression of neuroendocrine tumors. A therapy directed at IGFR mediated signaling pathways has potential for conferring enhanced anti-tumor activity. We evaluated the safety and efficacy of MK-0646, a monoclonal antibody (mab) that blocks the insulin-like growth factor receptor (IGF-1R), as monotherapy in metastatic well differentiated neuroendocrine patients. Methods: A phase II study was performed in which patients received MK-0646 at a dose of 10 mg/kg iv over 1 hour weekly. Archived pretreatment tumor tissue was obtained for putative biomarkers. Results: A total of 25 patients were treated (15 carcinoid, 10 islet cell carcinoma) female, 40%; median age, 61 years, (range 36-82). No antitumor activity was seen in these 25 patients treated with MK-0646 monotherapy. Five patients achieved stable disease for 24 weeks or longer defined by RECIST criteria (range 6.25-10.5 months). The most common serious adverse event (SAE) thought to be potentially related to MK-0646 was hyperglycemia (7 patients, 25%). Other SAEs included one grade 2 infusion-related reaction (4%), and 2 patients with grade 3 fatigue (8%). Conclusions: MK-0646 alone was well tolerated with the exception of hyperglycemia that was manageable with antihyperglycemic medications, however, the degree of activity seen was insufficient to warrant further study as a monotherapy in well differentiated neuroendocrine tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Alchemia, Biothera, Delcath, ImClone Systems, Merck, Novartis, Roche Pfizer Amgen, Biothera, Bristol-Meyers Squibb, Curetech, Genentech, ImClone Systems, Lilly, Merck, Pfizer, Roche, Tercica