Neoadjuvant PD-1 inhibitor (Sintilimab) in Non-Small Cell Lung Cancer

Abstract Background Programmed death receptor-1 (PD-1) inhibitors have shown efficacy in first line treatment of non-small cell lung cancer (NSCLC), however, evidence of PD-1 inhibitor as neoadjuvant treatment is limited. This is a phase 1b study to evaluate the safety and outcome of PD-1 inhibitor in neoadjuvant setting. Methods Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1/22). Surgery was performed between day 29-43. PET-CT was obtained at baseline and prior to surgery. Primary endpoint was safety. Efficacy endpoints included rate of major pathologic response (MPR) and objective response rate (ORR). PD-L1 expression was also evaluated. (Registration Number: ChiCTR-OIC-17013726). Results Forty patients enrolled, all of whom received 2 doses of sintilimab, and 37 underwent radical resection. Twenty-one (52.5%) patients experienced neoadjuvant treatment-related adverse events (TRAEs). Four (10.0%) patients experienced grade 3-4 neoadjuvant TRAEs, and one patient had grade 5 TRAE. Eight patients achieved radiological partial response, resulting in an ORR of 20.0%. Among 37 patients, 15 (40.5%) achieved MPR, including 6 (16.2%) with a pathologic complete response in primary tumor and 3 (8.1%) in lymph nodes as well. Squamouse cell NSCLC exhibited superior response compared to adenocarcinoma (MPR: 48.4% VS. 0%). Decrease of maximum standardized uptake values (SUVmax) after sintilimab treatment correlated with pathological remission (p Conclusion Neoadjuvant sintilimab was tolerable for NSCLC patients and 40.5% MPR rate is encouraging. The decrease of SUVmax after sintilimab might predict pathologic response.