| 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. Female subjects should be using highly effective contraceptive measures, and must have
a negative pregnancy test and not be breast-feeding 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 more than 50 years and amenorrheic for at least
12 months following cessation of all exogenous hormonal treatments
- Women under 50 years old would be consider postmenopausal if they have been
amenorrheic 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
4. Male subjects should be willing to use barrier contraception (see Restrictions,
Section 3.8)
5. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
with local confirmation of the presence of EGFR TKI-sensitizing mutation (EGFR exon 19
deletion or L858R mutation), either alone or in combination with other EGFR mutations
excluding EGFR exon 20 insertion mutation
6. Mandatory provision of fresh tumor sample before osimertinib via a biopsy or surgical
resection
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8. Patients must have a life expectancy = 12 weeks.
9. At least one lesion, not previously irradiated, that can be accurately measured at
baseline as = 10 mm in the longest diameter (except lymph nodes which must have short
axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and
which is suitable for accurate repeated measurements
10. Provision of informed consent for whole-genome and whole-exome sequencings
Exclusion Criteria:
1. Involvement in the planning and/or conduct of the study
2. Previous treatment with an EGFR TKI
3. Patients with different kinds of cancers within 5 years or with malignants
simultaneously (except completely cured skin basal cell carcinoma or uterine cervical
cancer)
4. Treatment with an investigational drug within five half-lives or 3 months. Patients
receiving an radiotherapy targeting brain metastasis or spinal cord compression within
2 weeks before the beginning of study treatment, receiving an wide field radiotherapy
over 30% of spinal cord reactivity or who are unrecovered from radiotherapy toxicity
5. Patients currently receiving (or unable to stop use prior to receiving the first dose
of study treatment) medications or herbal supplements known to be strong inducers of
CYP3A4 (at least 3 weeks prior). All patients must try to avoid concomitant use of any
medications, herbal supplements and/or ingestion of foods with known inducer effects
on CYP3A4
6. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of
starting study treatment, with the exception of alopecia and grade 2, prior
platinum-therapy-related neuropathy
7. 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
8. Patients with spinal cord compression, symptomatic or unstable brain metastases except
for those patients who have completed definitive therapy and have had a stable
neurological status for at least 2 weeks after completion of definitive therapy.
Patients who may be on corticosteroids to control brain metastases if they have been
on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are
clinically asymptomatic are eligible
9. 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
10. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) > 470 msec obtained from 3
electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc
value
- Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG e.g. complete left bundle branch block, third degree heart block and
second degree heart block.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalaemia, congenital long QT syndrome, family
history of long QT syndrome or unexplained sudden death under 40 years of age in
first degree relatives or any concomitant medication known to prolong the QT
interval and cause Torsades de Pointes.
11. Past medical history of interstitial lung disease, drug-induced interstitial lung
disease, radiation pneumonitis which required steroid treatment, or any evidence of
clinically active interstitial lung disease
12. Inadequate bone marrow reserve or organ function (as demonstrated by any of the
following laboratory values: absolute neutrophil count <1.5 x 109/L; platelet count
<100 x 109/L; haemoglobin <90 g/L; alanine aminotransferase >2.5 times ULN if no
demonstrable liver metastases or >5 times ULN in the presence of liver metastases;
aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5
times ULN in the presence of liver metastases; total bilirubin >1.5 times ULN if no
liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome
[unconjugated hyperbilirubinaemia] or liver metastases; serum creatinine >1.5 times
ULN concurrent with creatinine clearance <50 mL/min [measured or calculated by
Cockcroft and Gault equation]-confirmation of creatinine clearance is only required
when creatinine is >1.5 times ULN
13. History of hypersensitivity to any of the active or inactive excipients of osimertinib
or drugs with a similar chemical structure or class to osimertinib
14. Patients who are pregnant or breast-feeding
15. 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
16. Previous allogeneic bone marrow transplant
17. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the
genetic sample collection
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