We raise the hypothesis that a STOP and GO strategy with induction by double immunotherapy Nivolumab + Ipilimumab combination during 6 months, followed by observation in patients with disease control (DC) at 6 months, would not be inferior to immunotherapy combination continuation until progression or unacceptable toxicity, in terms of progression-free survival, allowing lower toxicities cumulative rates, better quality of life and lower costs. Such strategy should not penalize overall survival, provided resuming immunotherapy at disease progression before second-line platinum-based chemotherapy.
This is an open-label, randomized, phase III study in adult (≥18 years) patients, with stage IV non-small cell lung cancer, PD-L1 positive tumors, previously untreated for advanced disease. Subjects will first be locally assessed for PD-L1 expression, using 1% cut-off. Patients with enough tumor samples for central PD-L1 expression assessment, will be given first-line Nivolumab+Ipilumumab combination as followed: Nivolumab administered IV over 30 minutes at 3 mg/kg every 2 weeks combined with Ipilimumab administered IV over 30 minutes at 1 mg/kg every 6 weeks.
Only patients with DC (objective response or stable disease), confirmed at 6 months, after a 1rst tumor evaluation at 3 months or beyond in case of pseudo-progression needing tumor reassessment, and without drug-related toxicity commanding treatment discontinuation will be randomized 1:1 either to continuation of Nivolumab+Ipilumumab combination until disease progression or unacceptable toxicity, or to clinical and radiological observation from week 24.
Subjects receiving Nivolumab+Ipilimumab beyond investigator assessed progression must also continue tumor assessments until treatment discontinuation.
Enrollment will end after approximately 868 subjects have been randomized (25/months). The primary endpoint of the study is Progression-Free Survival.
Clinical trial identification
Legal entity responsible for the study
IFCT (French Cooperative Thoracic Intergroup).
All authors have declared no conflicts of interest.