LBA37 A randomized, multicentric phase II study of preoperative nivolumab plus relatlimab or nivolumab in patients with resectable non-small cell lung cancer (NEOpredict-Lung)

Abstract

Preoperative immune checkpoint inhibitor therapy (PICIT) is a promising approach in curative treatment of non-small-cell lung cancer (NSCLC). This study explores the feasibility and efficacy of targeting PD-1 and LAG-3 prior to resection. Patients with histologically confirmed NSCLC stage IB, II or IIIA (UICC 8th edition) were randomized to receive two preoperative doses (q14d) of nivolumab (240 mg, arm A), or nivolumab (240 mg) plus relatlimab (80 mg, arm B). The primary study endpoint was the feasibility of curatively intended surgery within 43 days of start of PICIT. Secondary endpoints include pathological and radiological response rates, disease-free and overall survival rates (DFS, OS) and safety. Exploratory endpoints are addressed by translational research. From March 4, 2020 to July 15, 2022, 60 patients have been randomized. The primary endpoint was met by all patients. R0 resection rate was 98%, excluding 2 patients with pleural carcinosis, which had been undetected by preoperative imaging. PICIT-related adverse events were as expected with grade ≥ 3 events in 4 (arm A) and 2 (arm B) patients. Two patients treated in arm A died within 90 days of surgery. The 12 months OS rate across both arms was 96% (95% CI: 83-99%), the DFS rate was 91% (78-97%). Radiological response rates were 11% (arm A) and 27% (arm B) per RECIST (full population), and 41% (arm A) and 38% (B) per PERCIST (30 patients from one center). Complete or major histopathological response rates were 28% (arm A) and 32% (arm B). In 60% (arm A) and 71% (arm B) of resections after PICIT ≤ 50% vital tumor cells were observed.Table: LBA37Arm A (nivolumab)Arm B (nivolumab/relatlimab)n [female, male]30 (15, 15)30 (13, 17)Age [years] (median, range)64 (43-77)65 (43-81)Histology- adenocarcinoma1315- squamous109- adenosquamous22- other54UICC stage- I B910- II A61- II B1116- III A33- other10PD-L1 [TPS]- 0%89- 1-49%1215- ≥50%106 Open table in a new tab Preoperative immune checkpoint inhibition with nivolumab and relatlimab is safe and feasible in patients with curatively resectable NSCLC. High histopathological response rates indicate clinical efficacy, which merits further study supplementing with biomarker analyses for future patient selection.