• Provision of signed and dated, written informed consent form (ICF) prior to any study specific procedures.

• Male or female participants aged 18 years old and above.

• ECOG PS of 0-1.

• Life expectancy of at least 3 months at recruitment.

• Participants able to collect plasma samples at baseline.

• Newly diagnosed, and histologically documented locally advanced or metastatic non-squamous NSCLC with sensitizing EGFR mutations positive (either Exon 19 deletion or 21 L858R, confirmed by histology or cytology), and classified as stage IIIB, IIIC, IV or recurrent NSCLC which are not amenable to curative surgery or radiotherapy (per Version 8 of the International Association for the Study of Lung Cancer \[IASLC\] Staging Manual in Thoracic Oncology).

• Detectable EGFRm (Ex19del or L858R) in plasma ctDNA by central Super ARMS PCR testing at the time of screening.

• Participants must have untreated advanced NSCLC and intend to receive osimertinib plus chemotherapy as first-line treatment. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior to receiving the first dose of study treatment.

• Participants with asymptomatic and stable central nervous system (CNS) metastases for at least 2 weeks (for those who received definitive therapy and steroids, a stable neurological status for at least 2 weeks after completion of the treatment is required) will be allowed, including leptomeningeal metastases.

⁃ At least 1 lesion, not previously irradiated that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis of ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumour assessment scans.

⁃ Patients with hepatitis B virus (HBV) are only eligible for inclusion if they meet all the following criteria:

∙ Demonstrated absence of hepatitis C virus (HCV) co-infection or history of HCV co-infection

‣ Demonstrated absence of human immunodeficiency virus (HIV) infection

‣ Participants with active HBV infection are eligible if they are:

• Receiving anti-viral treatment for at least 6 weeks prior to study treatment, HBV DNA is suppressed to \<100 IU/mL and transaminase levels are below upper limit of normal (ULN).

‣ Participants with a resolved or chronic HBV infection are eligible if they are:

• Negative for hepatitis B surface antigen (HBsAg) and positive for hepatitis B core antibody \[anti-HBc IgG or total anti-HBc Ab\]. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment.

⁃ or

‣ Positive for HBsAg, but for \> 6 months have had transaminases levels below ULN and HBV DNA levels below \<100 IU/mL or below the detectable limit of locally available test kit (i.e., are in an inactive carrier state). In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment.

⁃ Patients with HIV are only eligible for inclusion if they meet all the following criteria:

∙ Demonstrated absence of HBV/ HCV co-infection

‣ Undetectable viral RNA load for 6 months

‣ CD4+ count of \>350 cells/μL

‣ No history of AIDS-defining opportunistic infection within the past 12 months

‣ Stable for at least 4 weeks on the same anti-HIV medications

⁃ Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:

∙ Post-menopausal defined as aged 50 years or more and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.

‣ Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution.

‣ Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

⁃ Male participants must be willing to use barrier contraception.