Surgical outcomes of patients with resectable non-small-cell lung cancer receiving neoadjuvant immunotherapy with nivolumab plus relatlimab or nivolumab: Findings from the prospective, randomized, multicentric phase II study NEOpredict-Lung

8500 Background: Feasibility of surgical resection for non-small-cell lung cancer (NSCLC) after preoperative immune checkpoint inhibitor therapy (PICIT) with PD-1/PD-L1 and CTLA-4 inhibitors has been established. This study reports the first data on surgery after preoperative LAG-3 inhibition in NSCLC patients. Methods: 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). Primary study endpoint was the number of patients undergoing curatively intended surgery within 43 days of initiation of PICIT. Surgery was performed following the institutional standards. Outcomes and perioperative events were prospectively recorded. Results: 60 patients (29 female) were randomized 1:1 from 4/2020 to 7/2022. All patients were operated within 43 days after initiation of PICIT. Median age in arm A was 65 (43-78) years and 67 (44-81) years in arm B. Clinical UICC stages were similar between both arms. Central tumor location was present in 50% in arm A and 45% in arm B. R0 resection was achieved in 57 patients (95% ITT population, 98,3% curatively resected population). Two patients had pleural carcinosis only detected at surgery, and 1 patient had R1 resection. Resection was performed by lobectomy (n=23 and 24), bilobectomy (2 and 1), sleeve lobectomy (5 and 4) and combined lobectomy+segmentectomy (0 and 1). Surgical approach was either by videothoracoscopy (n=60% and 63,3%) or thoracotomy (n=40% and 36,6%). Conversion was required in 3 vs. 2 patients. Median operation time was 149 (77-234) and 165 (61-205) minutes. Median number of resected lymph nodes was 15 (3-52) and 10 (3-50). Intraoperative bleeding from the pulmonary artery was observed in 1 patient in each arm and was managed without sequelae. Postoperative complications occurred in 33,3% and 26,6%. Median hospital stay was 7 (2-22) and 5,5 (2-24) days. Complete or major histopathological response was observed in 27% and 30%. Overall perioperative 30-day mortality was 0%. No negative impact on adjuvant therapy was observed. The 12 months OS rate across both arms was 96% (95% Cl: 83-99%), the DFS rate was 91 % (78-97%). Conclusions: Curative surgical resection following neoadjuvant combined PD-1/LAG-3 inhibition was equally safe and feasible as after PD-1 inhibition alone. Perioperative course, complications rate and outcome are comparable to other neoadjuvant regimens. Standard adjuvant therapies can be safely administered in this setting. Clinical trial information: NCT04205552 .