Background: SCLC embodies 15-20% of lung cancers. Patients (pts) are staged with either limited or extensive disease; the standard front-line treatment for the latter is chemotherapy with carbo- or cisplatin combined with etoposide or irinotecan. Response rates are high with limited duration. Recurrence may be attributable to chemo-resistant tumor initiating cells (TICs). Delta-like protein 3 (DLL3) is an inhibitory Notch receptor ligand identified as a novel target in SCLC TICs. DLL3 is highly expressed in SCLC but not normal tissue. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate composed of a DLL3-targeting IgG1 monoclonal antibody tethered to a DNA cross-linking toxin. Rova-T has shown activity in recurrent/relapsed ED SCLC patients (Rudin et al., Lancet Oncol, 2016). Given DLL3 expression in TICs, exploration of Rova-T front-line maintenance strategies in ED SCLC is warranted. The postulated mechanism of action of Rova-T and its clinical activity indicate potential to improve progression-free and overall survival in this setting. Methods: This is a Phase 3, randomized, double-blind, placebo-controlled, international study (NCT03033511, no pts enrolled yet as of 7 February 2017). Approximately 740 ED SCLC pts will be enrolled to include ~480 pts with high DLL3 expression. Eligibility: pts ≥ 18 years; histologically or cytologically confirmed ED SCLC with ongoing clinical benefit (complete/partial response or stable disease) after 4 cycles of 1^st line platinum-based therapy; definitively treated CNS metastases allowed; > 3 but ≤ 9 wks between the administration of the last cycle of platinum-based chemotherapy and randomization; available tumor tissue for DLL3 expression testing; ECOG performance score 0-1. Pts will be randomly assigned 1:1 to receive 0.3 mg/kg Rova-T or placebo on Day 1 of each 6-wk cycle, omitting every 3^rd cycle. Primary objectives: determine if Rova-T improves progression-free and overall survival. Secondary objectives: assess Rova-T antitumor activity by determining objective response rate, clinical benefit rate, duration of response, and changes in pt reported outcomes. Clinical trial information: NCT03033511