Clinical Trial Finder

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:

• - a.

Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR.

• - b.

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.

This is a Phase II single center, open-label, single arm study in patients with advanced non-small cell lung cancer (stage IV) with brain metastases. Patients will be treated with combination of Pembrolizumab 200mg plus platinum doublet based on histology subtypes. After the 4 cycles of combination phase with cytotoxic chemotherapy, maintenance phase will be followed for maximum of 35 cycles. If the disease progression is observed in CNS only which can be controlled with local treatment, systemic treatment can be continued as beyond disease progression. Non-squamous cell carcinoma: 4 cycles of pemetrexed 500mg/m2 + carboplatin AUC 5.0 + pembrolizumab 200mg every 3 weeks Followed by pemetrexed 500mg/m2 + pembrolizumab 200mg every 3 weeks up to 35 cycles. Squamous cell carcinoma: 4 cycles of paclitaxel 200mg/m2 + carboplatin AUC 6.0 + pembrolizumab 200mg every 3 weeks Followed by pembrolizumab 200mg every 3 weeks up to 35 cycles

Arms

Experimental: Non-squamous cell carcinoma

4 cycles of pemetrexed 500mg/m2 + carboplatin AUC 5.0 + pembrolizumab 200mg every 3 weeks Followed by pemetrexed 500mg/m2 + pembrolizumab 200mg every 3 weeks up to 35 cycles

Experimental: Squamous cell carcinoma

4 cycles of paclitaxel 200mg/m2 + carboplatin AUC 6.0 + pembrolizumab 200mg every 3 weeks Followed by pembrolizumab 200mg every 3 weeks up to 35 cycles

Interventions

Drug: - Pemetrexed, Carboplatin, Pembrolizumab

Pemetrexed 500mg/m2 Carboplatin AUC 5.0 Pembrolizumab 200mg

Drug: - Paclitaxel, Carboplatin, Pembrolizumab

Paclitaxel 200mg/m2 Caboplatin AUC 6.0 Pembrolizumab 200mg