A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer

Concordance of EGFRm Status Between Tumor Tissue DNA and Patient-matched Plasma-derived ctDNA (Mutation Ex19Del or L858R)

Comparing the baseline central cobas® EGFR Mutation Test V2 between tumor tissue DNA and matched plasma ctDNA results (excluding invalid results). Since this endpoint uses pre-randomization data, treatment arms were combined for the analysis.

Time frame: Screening/Baseline

Concordance of EGFR Mutation Status Between the Local and Central Test Results From Baseline Tumor Samples (Mutation Ex19Del or L858R)

Comparing the local EGFR mutation test result used for patient selection with the retrospective baseline central cobas® EGFR Mutation Test V2 results (excluding invalid results). Since this endpoint uses pre-randomization data, treatment arms were combined for the analysis.

Time frame: Screening/Baseline

Change From Baseline in EORTC QLQ-C30 Primary Subscale Scores (Neoadjuvant Period)

Average change from baseline across all visits are reported. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (random effect), treatment, visit (fixed effect \& repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction. EORTC QLQ-C30 has 30 questions and questions are combined to produce symptom scales, individual symptom items, functional scales, and global health status (GHS)/quality of life (QoL). Each of the scale/items range from 0-100 after a linear transformation. Positive change from baseline scores on the GHS/QoL and functioning scales indicate improvement on health status/function, and negative change scores on symptom scales/items represent less symptom severity/improvement on symptom status.

Time frame: Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days ).

Change From Baseline in EORTC QLQ-LC13 Primary Subscale Scores (Neoadjuvant Period)

Average change from baseline across all visits are reported. The analysis was performed using a MMRM analysis on the change from baseline in the score at each visit, including subject (as a random effect), treatment, visit (as fixed effect and repeated measure) and treatment by visit interaction as explanatory variables, with the baseline score as a covariate along with the baseline score by assessment interaction. EORTC QLQ-LC13 has 13 questions and scores range from 0-100 after a linear transformation. Questions assess cough, hemoptysis, dyspnea, site specific pain, sore mouth, dysphagia, peripheral neuropathy, and alopecia and pain medication. While the QLQ-LC13 includes more scales, only the Coughing, Pain in chest, and Dyspnea subscale scores were analyzed for this endpoint. Negative change from baseline scores indicates less symptom severity, and thus improvement on health status.

Time frame: Assessed at baseline, Cycle 2 Day1, Cycle 3 Day1, and Pre-surgical assessment (on D64, -1 to +21 days).

PK Plasma Concentrations of Osimertinib

Summary of plasma concentrations (nM) of Osimertinib

Time frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)

PK Plasma Concentrations of AZ5104

Summary of plasma concentrations (nM) of AZ5104

Time frame: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)