Final survival outcomes and exploratory biomarker analysis from the randomized, phase 2 neoSCORE trial: Two versus three cycles of neoadjuvant sintilimab plus chemotherapy for resectable non-small cell lung cancer.

8048 Background: In the neoSCORE trial (NCT04459611), three cycles of neoadjuvant sintilimab plus chemotherapy achieved a numerically higher major pathological response (MPR) rate compared to two cycles. However, the relationship between MPR and survival in resectable non-small cell lung cancer (NSCLC) patients receiving neoadjuvant immunotherapy is not currently fully elucidated. Furthermore, reliable predictive biomarkers are still lacking. Here, we report the survival and biomarker results of the study. Methods: Eligible patients with stage IB-IIIA resectable NSCLC were randomized 1:1 to receive either two or three cycles of neoadjuvant treatment with sintilimab (200mg) plus platinum-doublet chemotherapy (Q3W). After surgery, patients received totally four doses of perioperative immuno-chemotherapy. The primary endpoint was the MPR rate. Secondary endpoints included the complete pathological response (pCR) rate, objective response rate (ORR), 2-year disease-free survival (DFS) rate, 2-year overall survival (OS) rate, and safety. Tumor samples (n = 19) were obtained for immune biomarker analysis via mass cytometry time of flight (CyTOF). Multiplexed immunofluorescence (mIF) was performed on FFPE tumor samples (n = 42). Results: At the data cutoff (15/1/2024), 55 patients received neoadjuvant immuno-chemotherapy and underwent surgical resection, with a median follow-up of 36.1 months. DFS (HR = 1.25, P= 0.595) and OS (HR = 0.88, P= 0.830) were similar between the two-cycle and three-cycle groups. The median DFS and OS were not reached in both groups. The 2-year DFS rate in the two-cycle and three-cycle groups were 76.9% and 65.5%, and the 2-year OS rates were 84.6% and 86.2%, respectively. In a multivariable Cox analysis including clinical characteristics, therapy, and pathological response, only MPR was significantly associated with longer DFS (HR = 0.32, P= 0.044). The AUC for the percentage of residual viable tumor in predicting DFS was 0.649 ( P= 0.061). CyTOF analysis demonstrated that increased infiltration of CD8+CD38+CD103- T cells after neoadjuvant immuno-chemotherapy was significantly associated with MPR ( P= 0.035). The mIF confirmed that patients achieving MPR showed higher frequencies of CD8+CD38+CD103- T cells than those without MPR ( P= 0.005). Additionally, patients with higher proportions of CD8+CD38+CD103- T cells had a trend towards improved DFS (HR = 0.39, P= 0.061) and OS (HR = 0.45, P= 0.259). Conclusions: Neoadjuvant sintilimab plus chemotherapy was feasible and demonstrated a robust and persistent survival benefit in resectable NSCLC. MPR was associated with improved DFS. Increased CD8+CD38+CD103- T cells were associated with MPR, with a trend towards a better survival benefit, suggesting that it could be a promising predictive biomarker. Clinical trial information: NCT04459611 .