Non-Small Cell Lung Cancer (NSCLC) Clinical Trials

‣ In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• The patient has metastatic EGFR-mutated NSCLC and is treated with osimertinib as part of regular care with CT-confirmed stable disease or better. Patients with (signs of) disease progression, are also eligible if their treating physician deems the treatment to be appropriate beyond progression and the expected osimertinib treatment duration is at least 1 month.

• The patient has an European Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.

• The patient is 18 years of age or older.

• The patient is able and willing to sign informed consent prior to any tests or procedures.

• The patient is able and willing to undergo additional blood sampling for e.g. therapeutic drug monitoring.

• The patient is able and willing to undergo lumbar punctions to obtain CSF.

• The patient must meet the criteria stated in the approved regulatory indication(s) for osimertinib where the clinical study will be performed and agree to the restrictions, monitoring, and dose-adjustment criteria stipulated in the associated product label.

• The patient does not harbour the ABCG2 34G\>A single nucleotide polymorphism.

• The patient does not have any central nervous system (CNS) metastases.

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

∙ Demonstrated absence of HCV co-infection or history of HCV co-infection

‣ Demonstrated absence of 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 ULN.

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

⁃ Negative for HBsAg and positive for hepatitis B core antibody \[anti-HBc IgG or total anti-HBc Ab\]. In addition, patients should be referred to a local hepatologist and treated as per local guidelines. 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

⁃ Patients must be willing to use protocol specified method of contraception during treatment with osimertinib and 6 weeks tafter the lost dose of osimertinib.

∙ Females who are not abstinent (in line with the preferred and usual lifestyle choice of the patient) and intend to be sexually active with a male partner 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