A Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Resectable Non-Small Cell Lung Cancer (NSCLC) - Lung Cancer Mutation Consortium (LCMC3)

ORR was defined as percentage of participants with complete response (CR) or partial response (PR) as determined by the investigator using RECIST v.1.1, assessed in the programmed death ligand 1 (PD-L1) positive (participants with combined tumor cell (TC)/ immune cell (IC) score categorized as TC1/2/3 or IC1/2/3) and PD-L1 negative (participants with TC/IC score was categorized as TC0 and IC0) groups. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages have been rounded off to the nearest decimal point.

Major pathologic response (MPR) was defined as ≤10% of viable tumor cells, as scored by a pathologist, based on surgical resection as defined by prior studies. MPR was assessed based on participants tumor cell (TC) and immune cell (IC) score. The participants were considered as PD-L1- positive if their combined TC/IC score was categorized as TC1/2/3 or IC1/2/3 and the participants were considered PD-L1 negative if TC/IC score was categorized as TC0 and IC0. Percentages have been rounded off to the nearest decimal point.

An adverse event (AE) was defined as any untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).

MPR was defined as ≤10% of viable tumor cells in the surgical resection as scored by a pathologist. Whole-exome sequencing (WES) was run, and the consequences of each mutation were determined using Ensembl Variant Effect Predictor (VEP). Mutation load (i.e. tumor mutation burden (TMB)) was defined as the number of variants altering protein sequence as outlined by VEP divided by 34 Megabase (MB) of assay target region. The final value was reported as number of mutations per megabase (mut/MB). It was divided into three groups: TMB <10 mut/MB; TMB ≥ 10 mut/MB to <16 mut/MB; and TMB ≥16 mut/MB. Percentages have been rounded off to the nearest decimal point.

MPR was defined as ≤10% of viable tumor cells in the surgical resection as scored by a pathologist. MPR was analysed by neoantigen score, which was assessed based on the number of highly immunogenic, expressed neoantigens detected at baseline. Median splits were applied for analyses of MPR. Neoantigen scores >/= 73 (i.e. >/= 73 highly immunogenic, expressed neoantigens detected at baseline) were considered as high scores, and scores <73 (i.e. <73 highly immunogenic, expressed neoantigens detected at baseline) were considered as low neoantigen scores. Percentages have been rounded off to the nearest decimal point.

MPR was defined as ≤10% of viable tumor cells in the surgical resection as scored by a pathologist. MPR was analysed by gene set variation analysis (GSVA) scores. Bulk ribonucleic acid (RNA) from baseline tumor samples were assessed using GSVA for a T effector cell (Teff) signature comprising the following genes: cluster of differentiation 8A (CD8A), eomesodermin (EOMES), granzyme A (GZMA), T-box transcription factor 21 (TBX21), interferon-gamma (IFNG), granzyme B (GZMB), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10). Tertile splits were applied to GSVA scores, categorized as lower, middle, and upper scores, which indicated the relative levels of gene set expression in the baseline tumor samples. Percentages have been rounded off to the nearest decimal point.

MPR was defined as ≤10% of viable tumor cells in the surgical resection as scored by a pathologist. MPR was analysed by gene expression signatures. Bulk RNA from baseline tumor samples were assessed using xCell immune score. Tertile splits were applied to xCell immune scores, categorized as lower, middle, and upper scores, which indicated the relative levels of immune cell gene expression in the baseline tumor samples. Percentages have been rounded off to the nearest decimal point.