OA06.06 Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study

Neoadjuvant immune checkpoint inhibitor therapies are well tolerated and may be of benefit in early-stage non-small cell lung cancer (NSCLC). Here we report clinical biomarker data from the Phase II LCMC3 (NCT02927301) study evaluating pre-operative treatment with atezolizumab (anti-PD-L1) patients untreated stage IB to IIIB resectable NSCLC. Patients had IB-IIIB NSCLC ECOG 0/1. received neoadjuvant 1200 mg intravenously every 3 weeks for ?2 cycles followed by surgical resection (day 40±10). Those could continue adjuvant ?12 months. The primary endpoint was major pathological response (MPR; ?10% viable tumor cells) at surgery without known EGFR/ALK mutations. Secondary endpoints included MPR PD-L1 status, mutation burden (TMB), adverse events (AEs), including treatment-related (TRAE) immune-related (irAE). Biomarker analyses multiplex immunofluorescence (mIF) image analysis, whole exome sequencing, RNA sequencing multi-parameter flow cytometry. 181 patients, whom 159 (Table). In alterations, 30/147 (20.4% [95% CI: 14%-28%]) achieved 10/147 (6.8% 3%-12%]) complete response. pre-surgery ORR (RECISTv1.1) 7% (11/159), all partial responses. 143 (90%) stable disease 4 (3%) progressive (missing RECIST assessment, n=1). AEs occurred 178/181 (98%) leading discontinuation 15/181 (8%), TRAEs 122/181 (67%) irAEs 75/181 (41%). associated status (clone 22C3), 16% TPS<1% 29% TPS?1% (P=0.117); 14% TPS<50% 37% TPS?50% (P=0.009). mIF showed that increased ratio CD3+/CD8+ GZMB+/CD8+ T-cells CD3+/FOXP3+ cells both (n=45) stromal (n=44) compartments, suggesting a shift toward T-cell activation. not observed EGFR mutations (n=7; 1 additional patient did have surgery) or ALK fusions (n=5). Median TMB 7.2 mutations/Mb (range, 0.8-43.5) (n=53), higher trended better STK11/LKB1 KEAP1 were more frequent non-MPR ongoing. trial met its 20% Data suggest positively expression negatively alterations. Ongoing comprehensive will provide insights into mechanisms immunotherapy cancers.Tabled 1Baseline characteristicsUnderwent surgeryNo (N = 22)Enrolled dosed 181)Achieved 30)No determined 129)Median age (range), y67 (39-83)65 (37-82)68 (46-81)65 (37-83)Female, n (%)23 (77)56 (43)14 (64)93 (51)Race, (%)White24 (80)105 (83)16 (73)145 (81)Black African American3 (10)7 (6)3 (14)13 (7)Asian1 (3)7 (6)1 (5)9 (5)Unknown2 (7)8 (6)2 (9)12 (7)Squamous histology, (%)14 (47)45 (35)10 (46)69 (38)Clinical stage, (%)IB3 (10)12 (9)1 (5)16 (9)IIA3 (10)16 (12)1 (5)20 (11)IIB9 (30)43 (33)8 (36)60 (33)IIIA12 (40)49 (38)10 (46)72 (39)IIIB3 (10)9 (7)2 (9)14 (8)Tobacco use, (%)Current12 (40)16 (12)7 (32)35 (19)Former16 (53)99 (77)13 (59)128 (71)Never2 (7)14 (11)2 (9)18 (10)TPS screening, (%)? 5013 (43)25 (19)2 (9)40 (22)? < 501 (3)16 (5)18 (10)< 17 (23)43 (36)58 (32)Unknowna9 (30)45 (35)11 (50)65 (36)STK11/LKB1 mutation, (%)bNo17 (57)54 (41)3 (14)74 (41)Yes1 (3)8 (6)0 (0)9 (5)Unknowna12 (40)67 (52)19 (86)98 (54)KEAP1 (%)bNo16 (53)55 (43)3 (41)Yes2 (7)7 (5)0 (54)SafetyAllGrade 3-4Grade 5Any AE, (%)178 (98)75 (41)6 (3)AE discontinuation, (%)15 (8)10 (1)TRAE, (%)122 (67)29 (16)1 (1)irAE, (%)75 (41)16 (1)TPS, proportion score; measured immunohistochemical 22C3 assay. Analysis ongoing time abstract preparation. b these groups, dual None MPR. Open table new tab