| Eligibility |
Inclusion Criteria:
1. Provision of informed consent prior to any study specific procedures
2. Male or female must be > 19 years of age.
3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
with local confirmation of the presence of the EGFR exon 20 insertion mutation
4. Disease progression while on standard chemotherapy (platinum doublet chemotherapy or
single-agent chemotherapy in selected patients)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
6. Patients must have a life expectancy = 12 weeks
7. Females should be using adequate contraceptive measures, should not be breast feeding
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:
8. Male patients should be willing to use barrier contraception
9. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
10. At least one measurable lesion
11. Provision of archival FFPE tissue
12. Provision of informed consent for translational genetic research
Exclusion Criteria:
1. Involvement in the planning and/or conduct of the study (applies to both sponsor staff
and/or staff at the study site)
2. Previous treatment with osimertinib (3rd generation EGFR TKIs such as olumtinib,
EGF816 etc)
3. Treatment with an investigational drug within five half-lives of the compound
4. Patients currently receiving (or unable to stop use prior to receiving the first dose
of study treatment) medications or herbal supplements known to be potent inhibitors of
CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior)
(Appendix A). All patients must try to avoid concomitant use of any medications,
herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on
CYP3A4.
5. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the
exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
hypertension and active bleeding diatheses, which in the investigator's opinion makes
it undesirable for the patient to participate in the trial or which would jeopardise
compliance with the protocol, or active infection including hepatitis B, hepatitis C
and human immunodeficiency virus (HIV). Screening for chronic conditions is not
required.
7. Patients with symptomatic CNS metastases who are neurologically unstable; however,
those with asymptomatic CNS metastases who do not require steroids for at least 4
weeks prior to start of osimertinib are eligible.
8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid
treatment, or any evidence of clinically active ILD
9. Inadequate bone marrow reserve or organ function
10. QTc prolongation (mean resting corrected QTc > 470 msec)
11. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
swallow the formulated product or previous significant bowel resection that would
preclude adequate absorption of osimertinib
12. History of hypersensitivity to osimertinib (or drugs with a similar chemical structure
or class to osimertinib) or any excipients of these agents
13. Males and females of reproductive potential who are not using an effective method of
birth control and females who are pregnant or breastfeeding or have a positive (urine
or serum) pregnancy test prior to study entry
14. Judgment by the Investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and requirements
15. Previous allogeneic bone marrow transplant.
16. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the
genetic sample collection.
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