Inclusion Criteria:
1. Male/female participants who are at least 19 years of age on the day of signing
informed consent with histologically confirmed diagnosis of stage IV non-small cell
lung cancer with brain metastases will be enrolled in this study.
2. Must have at least one intracranial target lesion. Intracranial lesion must be equal
or greater than the 10mm in longest diameter.
3. Have confirmation that EGFR or ALK-directed therapy is not indicated. 4. Have measurable disease based on RECIST 1.1 as determined by the local site
investigator/radiology assessment. Target lesions situated in a previously irradiated
area are considered measurable if progression has been demonstrated in such lesions.
Otherwise, previously treated with radiation is not considered as measurable lesion.
5. Have not received prior systemic treatment for their advanced/metastatic NSCLC.
Subjects who received adjuvant or neoadjuvant therapy are eligible if the
adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development
of metastatic disease.
6. Have a life expectancy of at least 3 months. 7. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Status.
8. Have adequate organ function. 9. Male participants: A male participant must agree to use a contraception during the
treatment period and for at least 120 days after the last dose of study treatment and
refrain from donating sperm during this period.
10. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR.
A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during
the treatment period and for at least 120 days after the last dose of study
treatment.
11. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
Exclusion Criteria:
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to IP
administration. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX 40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents prior
to IP administration as a metastatic disease treatment, including tyrosine kinase
inhibitor.
4. Had major surgery < 3 weeks prior to first dose. 5. No measurable CNS lesion other than CNS lesion treated with stereotactic radiotherapy
or surgery. 6. Had received whole brain radiotherapy or stereotactic radiotherapy to CNS disease.
7. Has received prior radiotherapy within 1 weeks of start of study intervention.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation to non-CNS disease.
8. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
9. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention.
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
11. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years. Participants with basal cell carcinoma of the skin, squamous
cell carcinoma of the skin, thyroid cancer or early gastric cancer or carcinoma in
situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially
curative therapy are not excluded.
12. Has known active carcinomatous meningitis.
13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
14. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment and is allowed.
15. Has a history of (non-infectious) pneumonitis that currently required steroids or has
current pneumonitis.
16. Has an active infection requiring systemic therapy.
17. Has a known history of Human Immunodeficiency Virus (HIV) infection.
18. Has a active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive with
HBV DNA positive) or known active Hepatitis C virus (defined as HCV RNA is detected)
infection. These patients can be participated with appropriate treatment and
prophylactic treatment based on the investigator's decision.
19. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator.
20. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
21. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
22. Has had an allogenic tissue/solid organ transplant.
