Background: In the CLARINET study (NCT00353496), LAN was associated with significantly prolonged progression-free survival (PFS) in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) of grade 1 or 2 (Ki-67 < 10%). Limited options are available for the treatment of patients with advanced lung NETs. The aim of the SPINET study is to evaluate the safety and antitumor efficacy of LAN 120 mg vs. PBO in these patients. Methods: SPINET is an international, multicenter, randomized, double-blind, PBO-controlled phase III study. Main inclusion criteria: adult patients with well-differentiated typical or atypical, metastatic and/or unresectable lung NETs, positive somatostatin-receptor imaging ( ≥ grade 2 Krenning scale), ≤ 1 course of chemotherapy, ECOG PS 0-1. A total of 216 patients will be enrolled from 80 sites across the USA, Canada, and Europe. Patients will be randomized 2:1 to receive either LAN (120 mg every 28 days) + best supportive care (BSC) or PBO + BSC, until progressive disease (PD)/death or unacceptable toxicity. Patients receiving PBO who experience PD may opt to receive LAN 120 mg in an open-label extension phase. All patients who experience PD will be followed to document survival, quality of life (QoL), and subsequent anticancer treatments. The primary endpoint, PFS (time from randomization to progressive disease [PD]/death), will be assessed based on central review using RECIST v1.1. Main secondary endpoints include PFS according to local review, objective response rates, overall survival, changes in plasma chromogranin (CgA) levels, LAN pharmacokinetics, QoL, and safety. This trial is active and registered with the EU Clinical Trials Register (EudraCT:2015-004992-62). Clinical trial information: 2015-004992-62.