Sintilimab plus docetaxel as second-line therapy of advanced non-small cell lung cancer without targetable mutations: a phase II efficacy and biomarker study

Background Single-agent immunotherapy is currently the recommended second-line therapy for patients with advanced non–small cell lung cancer (NSCLC) without targetable mutations; however, the objective response rate (ORR) remains low. This phase II study evaluated the efficacy of the combination therapy of sintilimab plus docetaxel and explored potential biomarkers for efficacy prediction. Methods Thirty patients with NSCLC without targetable mutations whose disease progressed from first-line platinum-based chemotherapy from October 2019 to December 2020 were enrolled in this single-arm, single-center, phase II trial. Sintilimab (200 mg) and docetaxel (75 mg/m 2 ) were administered every 3 weeks until progression. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarker analyses of blood and tissue samples were also performed. Results Among 30 patients, 11 patients had partial response, resulting in an ORR of 36.7%. The median PFS was 5.0 months (95%CI: 3.9–6.1) and OS was 13.4 months (95%CI: 5.6–21.2). The most common immune-related adverse event of any grade was hepatitis, observed in 23.3% (7/30) of patients. Treatment-emergent adverse events were manageable. Patients detected with high PD-L1 expression in circulating tumor cells (cutoff value ≥32.5% based on the median CTC-PD-L1 expression) achieved significantly higher ORR (60% versus 13.3%, p = 0.021) and significantly longer median PFS (6.0 versus 3.5 months, p = 0.011) and median OS (15.8 versus 9.0 months, p = 0.038) than those with low CTC-PD-L1 level. Patients detected with PD-L1 < 1% and CD8 ≥ 1% expression from their baseline tissue samples had significantly higher ORR (83.3% versus 12.5%, p = 0.026) but similar PFS ( p = 0.62) and OS ( p = 0.15). Conclusion This study demonstrated the effectiveness and safety of sintilimab plus docetaxel as a second-line treatment of NSCLC without targetable mutations after progression from first-line platinum-based chemotherapy. Trial registration This study was registered in the Clinical trials registry with ClinicalTrials.gov Identifier NCT03798743 (SUCCESS).