LBA84 Consolidation ipilimumab and nivolumab vs observation in limited stage SCLC after chemo-radiotherapy: Results from the ETOP/IFCT 4-12 STIMULI trial

Concurrent chemotherapy and thoracic radiotherapy (CRT) followed by prophylactic cranial irradiation (PCI) is the standard strategy in limited stage small cell lung cancer (LS-SCLC). STIMULI is a 1:1 randomized phase II international trial aiming to demonstrate superiority of consolidation immunotherapy treatment (C) vs observation (O) after standard CRT and PCI, in patients (pts) with LS-SCLC. C consisted of four cycles of nivolumab (1 mg/kg, Q3W) plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months (m). The trial was designed to test two co-primary endpoints, progression-free survival (PFS) by RECIST 1.1 criteria, and overall survival (OS), at 1-sided alpha of 1% and 4%, respectively. Trial enrollment closed prematurely due to slow accrual, after half the initial sample size. The statistical analyses plan was updated to address PFS as primary endpoint to be tested at the full 5% 1-sided significance level. 81 PFS events were needed to achieve a power of 80% for testing an HR of 0.57. Secondary endpoints include OS, time to treatment failure (TTF), and safety. 222 pts were enrolled with 153 randomized after completion of CRT and PCI, 78 to C and 75 to O. Median age 62 years, 60% males, 34%/65% current/former smokers, 31%/66% ECOG PS 0/1. In C, 40 PFS events were observed, with median PFS 10.7 m (95% CI 7.0-Not Estimable (NE)) vs 42 events and median 14.5 m (8.2-NE) in O, HR=1.02 (0.66-1.58), 2-sided p=0.93. Two-year PFS rate was 43% (31-55) and 40% (28-52) in C and O respectively. Median OS was not reached in C, while it was 31.6 m (26.1-NE) in O, HR=1.06 (0.61-1.86), p=0.83. One-year OS rate was 79% (68-87) in C and 89% (78-94) in O. Exploratory subgroups will be presented. In C, median time to treatment discontinuation was only 1.7 m. Grade≥3 AEs were experienced by 62% pts in C and 25% in O, with 4 and 1 fatal AE, respectively. PFS for LS-SCLC pts is not found different between C and O, possibly due to the short period on active treatment observed in the study.