Background: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%., Patients and Methods: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint., Results: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively., Conclusions: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results., Competing Interests: Disclosure SP reports personal fees from Abbvie, Bayer, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman–La Roche, Foundations Medicine, Janssen, Pharma Mar, Regeneron, Sanofi, Seattle Genetics, Takeda, Merck Serono, Merrimack, Medscape, Phosphoplatin Therapeutics, Beigene, Imedex and grants and personal fees from Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Illumina, Novartis, Pfizer, Merck Sharp and Dohme, outside the submitted work; all fees to the institution. UD reports personal fees from F. Hoffman–La Roche, outside the submitted work. MD reports personal fees from AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, F. Hoffman–La Roche, Merck Sharp and Dohme, Pfizer, and Takeda, outside the submitted work. SP reports personal fees from Amgen, AstraZeneca, Bayer, BeiGene, Blueprint Medicines, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, F. Hoffman–La Roche, GlaxoSmithKline, Guardant Health, Incyte, Janssen, Lilly, Merck KGaA, and Takeda, outside the submitted work. MR reports personal fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Lilly, Merck KGaA, Merck Sharp and Dohme, Mirati, Novartis, Pfizer, F. Hoffman–La Roche, and Regeneron, outside the submitted work. DMS reports grants, personal fees and non-financial support from AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, F. Hoffman–La Roche, during the conduct of the study; grants, personal fees and non-financial support from Boehringer-Ingelheim, Pfizer, and Takeda, grants and non-financial support from Lilly, outside the submitted work. OM reports personal fees from AstraZeneca, Merck Sharp and Dohme, Bristol-Myers Squibb, and Takeda, outside the submitted work. KN reports personal fees from Amgen, AbbVie, AstraZeneca, Bristol-Myers Squibb Belgium, and F. Hoffman–La Roche Belgium, outside the submitted work. AIM reports personal fees from Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol, F. Hoffman–La Roche, Merck Sharp and Dohme, Pfizer, and Takeda, outside the submitted work. JM reports other from Boehringer-Ingelheim, Bristol-Myers Squibb, F. Hoffman–La Roche, and Pfizer, outside the submitted work. JM reports grants and personal fees from AstraZeneca, F. Hoffman–La Roche, Pierre Fabre and personal fees from Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Hengrui, Merck, Merck Sharp and Dohme, and Pfizer, outside the submitted work. MF reports personal fees from AstraZeneca, Bristol-Myers Squibb, F. Hoffman–La Roche, and Merck Sharp and Dohme, outside the submitted work. FG reports grants and personal fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, F. Hoffman–La Roche, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Siemens, and Takeda, and personal fees from Abbvie, outside the submitted work. MM reports grants and personal fees from Bristol-Myers Squibb, Pierre Fabre, personal fees and non-financial support from AstraZeneca, Boehringer-Ingelheim, F. Hoffman–La Roche, Merck Sharp and Dohme, and personal fees from Kyowa Kirin, outside the submitted work. MPP reports grants, personal fees and non-financial support from AstraZeneca, Bristol-Myers Squibb, and F. Hoffman–La Roche, personal fees from Merck Sharp and Dohme, and Takeda, outside the submitted work. PM reports personal fees from Amgen, AstraZeneca, Bristol-Myers Squibb, F. Hoffman–La Roche, Merck Sharp and Dohme, Puma Biotechnology, Specialised Therapeutics and grants from AstraZeneca, and Bristol-Myers Squibb, outside the submitted work. RAS reports grants and personal fees from AstraZeneca, Bristol-Myers Squibb, F. Hoffman–La Roche, Merck Sharp and Dohme, Pfizer, and Novartis, grants from F. Hoffman–La Roche, Ipsen, Pierre Fabre, personal fees from Amgen, Blueprint, Boehringer-Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Regeneron, Seattle Genetics, and Sandoz, personal fees and other from Genentech/F. Hoffman–La Roche, Lung Cancer, Takeda, and other from CTR, outside the submitted work. CLP reports other from Amgen, AstraZeneca, F. Hoffman–La Roche, Lilly, Medscape, and Nanobiotix, and personal fees from PrimeOncology, outside the submitted work. DDR reports grants from AstraZeneca, Bristol-Myers Squibb, Olink, Philips Health, and Seattle Genetics, and outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)