1215O - SC Neoadjuvant atezolizumab (A) for resectable non-small cell lung cancer (NSCLC): Results from the phase II PRINCEPS trial

Neoadjuvant immune checkpoint inhibitors induce major pathologic response (MPR) rates in 17- 45% of NSCLCs. We report the results of a phase 2 trial of neoadjuvant A for NSCLC. Patient (pts) with clinical stage IA (≥ 2 cm)-IIIA non N2 NSCLC eligible for surgery, PS 0-1, received 1 injection of A (1200 mg IV D1) followed by surgery between D21-D28. The primary endpoint was the rate of pts without major toxicities or morbidities from D1 until 1 month after the surgery. Fresh tumour tissue was analysed within 4 hours after surgery. Response by RECIST1.1 and major pathological response (MPR; ≤10% viable tumour) were assessed. From December 2016 to February 2020, 30 pts were enrolled in two centres. The mean age of pts was 64, 50% were female, 7% never smokers, 83% had adenocarcinomas. Pathological stages were I (n=15, 50%), II (n=6, 20%) III (n=9, 30%). All pts had their planned surgery, none were delayed by >15 days. 29 had R0 resection, 1 had R1. Three pts experienced surgical complications: 1 respiratory distress grade 3 with sepsis grade 4, 1 heart block atrioventricular and 1 paresthesia grade 1. There was no grade 5 toxicity. Treatment-related adverse effects (TRAEs) included only one grade 1 parietal pain related to surgery. No RECIST radiological response and no MPR were observed. After A, 15/29 tumours were PD-L1 TC3 or IC3 based on the SP142 assay. 17/30 (56%) tumours had necrosis (med. 5% of tumour surface, 0-80). 20/29 cases had histopathological features of response according to the immune-related pathologic response criteria (irPRC), with isolated or combined features of immune activation (19/20), tissue repair (15/20) and/or tumour cell death (9/20).NGS (11 genes) was performed in 23 tumours resulting in 14 TP53 mutations (mut), 7 KRAS mutations , 3 EGFR mutations, 1 wild-type, 1 STK11 mutations (in a tumour with 80% necrosis). Surgery after one infusion of A was safe. The short delay between A and surgery might explain the absence of MPR.