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). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10045-0.