• Patient must have a pathologically-confirmed diagnosis of non-small cell lung cancer (NSCLC).

• Patient must have advanced disease, defined as IIIB (not amenable to definitive multi-modality therapy), IIIC, or IV (includes local or distant recurrent disease after a prior diagnosis of Stage I-III disease). All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 8th edition staging criteria.

• Patient tumor must have somatic activating sensitizing mutation in EGFR (e.g., but not limited to Exon 19 deletion, L858R, E709X, G719X, exon 19 insertions, L861Q, S768I). Patients with non-sensitizing mutations in EGFR (EGFR exon 20 insertions) are not eligible. Plasma, cytology, or tumor tissue can be utilized for standard of care mutation testing.

• Prior chemotherapy and/or immunotherapy administered as primary treatment for NSCLC before EGFR mutation was identified is allowed ≤ 45 days of study registration to allow for return of sequencing information.

• Prior treatment with osimertinib administered as primary treatment for NSCLC is allowed ≤ 30 days of study registration (prior treatment with any other EGFR TKI agent is not allowed).

• Patient must not be participating in EA5182 or any other cancer treatment trial. Osimertinib or osimertinib + chemotherapy/immunotherapy given as first-line treatment for this disease cannot be given as part of a clinical trial.

• Patients that have received prior radiation therapy in any setting for this disease are eligible.

• Adults age ≥ 18 years.