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

Major pathologic response was defined as ≤10% of viable tumor cells as scored by a pathologist, based on surgical resection as defined by prior studies. Percentages have been rounded off to the nearest decimal point.

Time frame: After surgery (approximately 10 weeks)

Population: The Primary Efficacy Population (PEP) included NSCLC participants who had received surgery after neoadjuvant treatment with atezolizumab, received at least one dose of the study drug, and who did not have Epidermal Growth Factor Receptor (EGFR) or Anaplastic Lymphoma Kinase (ALK) mutant tumors. The overall number analyzed was the number of participants with data available for analysis.

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).

Time frame: From first study dose of atezolizumab until 90 days after the last study dose of atezolizumab (up to 18 months)

Population: Safety population included all enrolled NSCLC participants who have received any dose of study drug.

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.

Time frame: Pre-surgery (Day 36 +/- 3 days), after 2 doses of neoadjuvant treatment with atezolizumab

Population: The overall number analyzed included participants in the PEP with non-missing ORR data and PD-L1 status. The PEP included participants with NSCLC who had received surgery after neoadjuvant treatment with atezolizumab, received at least one dose of the study drug, and who did not have EGFR or ALK mutant tumors. The number analyzed per row was the number of participants with data available for analysis in each PD-L1 group.

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.

Time frame: After surgery (approximately 10 weeks)

Population: The overall number analyzed included participants in the PEP with non-missing MPR data and PD-L1 status. PEP included participants with NSCLC who had received surgery after neoadjuvant treatment with atezolizumab, received at least one dose of the study drug, and who did not have EGFR or ALK mutant tumors. The number analyzed per row was the number of participants with data available for analysis in each PD-L1 group.

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.

Time frame: Up to 13 weeks

Population: The overall number analysed included participants in the PEP with non-missing MPR and GSVA score data. The PEP included participants with NSCLC who had received surgery after neoadjuvant treatment with atezolizumab, received at least one dose of the study drug, and who did not have EGFR or ALK mutant tumors. The number analyzed per row was the number of participants with data available for analysis in each GSVA score subgroup.

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.

Time frame: Up to 13 weeks

Population: The overall number analyzed included participants in the PEP with non-missing MPR and xCell immune score data. The PEP included participants with NSCLC who had received surgery after neoadjuvant treatment with atezolizumab, received at least one dose of the study drug, and who did not have EGFR or ALK mutant tumors. The number analyzed per row was the number of participants with data available for analysis in each xCell immune score subgroup.

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.

Time frame: Up to 13 weeks

Population: The overall number analyzed included participants in the PEP with non-missing MPR and TMB data. The PEP included participants with NSCLC who had received surgery after neoadjuvant treatment with atezolizumab, received at least one dose of the study drug, and who did not have EGFR or ALK mutant tumors. The number analyzed per row is the number of participants with data available for analysis in each TMB subgroup.

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.

Time frame: Up to 13 weeks

Population: The overall number analyzed included participants in the PEP with non-missing MPR and neoantigen score data. The PEP included those with NSCLC who had received surgery after neoadjuvant treatment with atezolizumab, received at least one dose of the study drug, and who did not have EGFR or ALK mutant tumors. The number analyzed per row is the number of participants with data available for analysis in each neoantigen score subgroup.