Background: Early stage non-small-cell lung cancer (NSCLC) could benefit from anti-programmed cell death-1 (PD-1) monotherapy; however, the survival profiles remain to be disclosed. Here, we presented the two-year follow-up outcomes from a phase 1b study of sintilimab, an anti-PD-1 inhibitor in the neoadjuvant setting of NSCLC. Methods: Treatment-naive pts with resectable NSCLC (stage IA–IIIB) received two cycles of sintilimab followed by surgical resection. Postoperative treatment of sintilimab was at the discretion of investigator. The primary endpoint was AE, and key secondary endpoints included major pathological response (MPR), disease free survival (DFS) rate of 1 year and 2 years, and overall survival (OS) rate of 2 years. Results: Among 40 enrolled pts, 36 (90%) underwent R0 resection and were included in the R0 resection population. By data cutoff (January 20, 2021), the median follow-up for DFS and OS for all the enrolled pts was 23.9 (IQR 20.5–24.4) months and 26.4 (IQR 24.2–29.0) months. A total of 12 (33.3%) pts experienced relapse, and 6 pts died. The 1-yr and 2-yr DFS rate was 91.7%/73.3%. The 2-yr OS rate for overall population and R0 population was 87.5%/91.7%, respectively. In the R0 resection population, the median DFS and OS were both not reached. Superior 2-year DFS rates were observed in pts who achieved MPR (MPR vs. Non-MPR: 86.7% vs. 63.8%). DFS of pts with non-squamous cell carcinoma tended to be shorter than that of pts with squamous cell carcinoma (HR 2.71 [95%CI 0.67–11.0], p=0.1479). Pts with tumor mutation burden (TMB) ≥10 mutations/Mb and PD-L1 tumor proportion score (TPS)≥50% tended to have a better 2-yr DFS rate compared to those with TMB<10 and TPS<50. [table] For the post-hoc event free survival (EFS) analysis, the same trend was observed with DFS among different subgroups, and patients with TMB ≥10 mutations/Mb had a significant improved EFS (HR 0.125[95% CI 0.02,1.03], P=0.0222). Conclusions: Anti-PD-1 monotherapy emerged to be a promising neoadjuvant therapeutic strategy for resectable NSCLC with improved clinical outcomes. MPR could serve as a surrogate efficacy biomarker in this setting. Clinical trial information: ChiCTR-OIC-17013726.

*, assessed by investigator per RECIST v1.1.