Background: Effective treatment options are limited in patients with metastatic NET. Temozolomide (TEM) alone and in combination with capecitabine is active in NETs, and has been shown to have immunomodulatory impact on lymphoid cells in patients with advanced cancers. Here we present the interim efficacy analysis of the NET cohort of our phase 2 trial of combination nivolumab and TEM in patients with advanced NET and small cell lung cancer. Methods: NCT03728361 is a non-randomized, two-cohort, single-institution, investigator-sponsored, open-label phase 2 study of nivolumab and TEM in patients with advanced or metastatic NET of any grade or primary site and recurrent/refractory small cell lung cancer. A total of 28 patients are planned to be treated in the NET cohort. Study treatment consists of nivolumab 480 mg intravenously every 4 weeks and TMZ 150 mg/m2 orally for 5 days out of a 28 day cycle. The primary endpoint is best overall response rate (ORR) by RECIST v1.1. It was pre-defined that an interim analysis would be performed after 15 patients, where ≥ 3 objective responses would be considered sufficient to continue accrual to a total of 28 patients. Adverse events were graded using CTCAE v5. Here we present the interim efficacy analysis after 15 patients were accrued in the NET cohort. Results: Twelve of 15 patients were evaluable for response (Table 1; 3 patients have not yet had response assessment). Best response was partial response (PR) in 3/12 (ORR 25%), stable disease in 8/12 patients (67%), and progressive disease in 1 patient (8%). Of the patients with PR, 1 had pancreatic (Ki-67: 80%), 1 had ampullary (Ki-67: 70%), and 1 had bronchial (Ki-67: 15%) NET. With a median follow up time of 6.9 months, progression-free survival and overall survival data are not mature. Serious adverse events occurred in 4 patients - one patient had grade 3 bronchopulmonary hemorrhage, 3 patients had grade 4 neutropenia and/or thrombocytopenia. There were no treatment-related deaths. Conclusions: Combination nivolumab and temozolomide demonstrated promising preliminary efficacy in NET in an interim analysis from an ongoing phase 2 trial, including responses in high grade tumors. Accrual is ongoing.