Johnson, Melissa LZvirbule, ZaneteLaktionov, KonstantinHelland, AslaugCho, Byoung ChulGutierrez, VanesaColinet, BenoîtLena, HerveWolf, MartinGottfried, MayaOkamoto, Isamuvan der Leest, CorRich, PatriciaHung, Jen-YuAppenzeller, ChristinaSun, ZhaowenMaag, DavidLuo, YanNickner, CarolineVajikova, AlenaKomarnitsky, PhilipBar, Jair2023-02-092023-02-092021-04-03http://hdl.handle.net/10668/17534Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, an atypical Notch ligand expressed in SCLC tumors. We evaluated the efficacy of Rova-T versus placebo as maintenance therapy in patients with extensive-stage-SCLC after platinum-based chemotherapy. MERU was a phase 3 randomized, double-blinded, placebo-controlled study. Patients without disease progression after four cycles of platinum-based, front-line chemotherapy were randomized in a 1:1 ratio to receive 0.3 mg/kg Rova-T or placebo (every 6 wk, omitted every third cycle). Primary efficacy end points were progression-free survival (PFS) evaluated by the Central Radiographic Assessment Committee and overall survival (OS) in patients with DLL3-high tumors. Median age of all randomized patients (N = 748) was 64 years; 78% had TNM stage IV disease. At futility analysis of the subset with DLL3-high tumors, the hazard ratio for OS was 1.07 (95% confidence interval: 0.84-1.36) favoring the placebo arm, with median OS of 8.5 and 9.8 months in the Rova-T and placebo arms, respectively; futility criteria were met. Rova-T significantly improved PFS versus placebo by investigator assessment (4.0 versus 1.4 mo, hazard ratio = 0.48, p  Because of the lack of survival benefit in the Rova-T arm, the study did not meet its primary end point and was terminated early. As a result, the Central Radiographic Assessment Committee evaluation of PFS was not performed. The frequency of grade greater than or equal to 3 and drug-related toxicities were higher with Rova-T versus placebo. Rova-T was associated with unique toxicities, such as pleural and pericardial effusions, photosensitivity reaction, and peripheral edema, which should be carefully considered in the population with extensive-stage-SCLC.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/DLL3MaintenancePhase 3Platinum-based chemotherapyRovalpituzumab tesirineSmall cell lung cancerAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBenzodiazepinonesDouble-Blind MethodHumansImmunoconjugatesLung NeoplasmsMiddle AgedPlatinumresearch article33823285open access10.1016/j.jtho.2021.03.0121556-1380http://www.jto.org/article/S1556086421020670/pdf