Multicenter phase 1b-2 trial of nintedanib plus nivolumab in pretreated patients with advanced or metastatic lung adenocarcinoma

Nivolumab and nintedanib are both established agents for pretreated NSCLC of adenocarcinoma histology. A multicenter phase 1b-2 trial in Germany evaluated the combination of nivolumab and nintedanib for patients with stage IIIB/IV adenocarcinoma NSCLC after one or two previous lines of systemic therapy with platinum-based chemotherapy with or without checkpoint inhibitors (CPI). Primary endpoints were safety and tolerability together with 6- and 9-months rates of progression-free survival (PFS). In phase 1b, the recommended phase 2 dose was determined to be nintedanib 200 mg twice daily with nivolumab 240 mg biweekly. PFS rates at 6 and 9 months for the 52 patients who received this combination were 25% (95% CI 14.3-37.3) and 11.5% (4.7-21.8), respectively. Median overall survival (OS) was 12.2 months (95% CI 8.1-18.4). High PD-L1 combined positive score and low PD-L1/low FGFR1 identified patients with prolonged Osat 36 months (70% and 40%, respectively), while low PD-L1/high FGFR1 was associated with shorter OS. CPI-rechallenged patients had better OS outcomes than those who were CPI-naïve (median OS 8.13 months versus 14.7 months; p=0.0493). The authors conclude that the combination of nivolumab and nintedanib was safe and feasible, whit promising OS for patients with high PD-L1 expression and for patients with previous immunotherapy.