Efficacy and Safety of Combination Therapy With Bojungikki-tang and Pembrolizumab Monotherapy in Patients With Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

1. Patients who voluntarily decided to participate and provided written consent, afterlistening and understanding the detailed explanation about the clinical trial

2. Adult male or female aged 19 years or older

3. Patients with histologically or cytologically confirmed advanced (stage IV)non-small cell lung cancer [according to TNM 8th edition] In case of recurrence,only extra-thoracic metastasis is allowed.

4. Patients planned for immune checkpoint inhibitor (Pembrolizumab) monotherapy asfirst-line treatment (Patients with PD-L1 tumor proportion score(TPS) ≥ 50% and noEGFR or ALK genomic tumor aberrations)

5. Life expectancy ≥ 3 months

6. ECOG (Eastern Cooperative Oncology Group) Performance Status score of 0~2

7. Patients with at least 1 measurable lesion as defined in RECIST V1.1

8. Patients with adequate bone marrow reserve or organ function as follows:

• Hemoglobin ≥ 9.0 g/dL

• Absolute neutrophil count (ANC) ≥ 1,500/㎕

• Platelet count ≥100× 10^3/㎕

• Serum creatinine ≤ 1.5x ULN or creatinine clearance ≥ 45 ml/min (measured usingstandard methods at the study site)

• ALT and AST ≤ 2.5× ULN Patients with liver metastasis: ALT and AST ≤ 5× ULN

• Total bilirubin ≤ 1.5× ULN Patients with liver metastasis or known Gilbertsyndrome(unconjugated hyperbilirubinemia): Total bilirubin ≤ 3× ULN

Exclusion Criteria:

1. Active brain metastases accompanied by clinically significant neurological symptomsor signs

2. Patients who diagnosed with another primary malignancy that affect non-small celllung cancer in the last 5 years However, effectively treated non-melanoma skincancer, carcinoma in situ of cervix, ductal carcinoma in situ of breast, thyroidcancer, or malignancies which were remained in remission during more than 3 yearsafter being treated effectively and considered cured are permitted.

3. Patients who treated with immune checkpoint inhibitor or anti-CTLA-4 within the last 6 weeks or systemic immunosuppressive medications within the last 2 weeks However,low-dose corticosteroids (prednisone ≤ 10 mg/day or an equivalent dose ofcorticosteroid within 7 consecutive days) are permitted at the investigator'sdiscretion.

4. Patients receiving thiazide or loop diuretics

5. Hypokalemia (less than 3.0 mEq/L)

6. Active interstitial lung disease requiring oral or intravenous steroid treatment

7. Patients with autoimmune disease requiring systemic treatment at the time ofenrollment

8. Uncontrolled diabetes mellitus at the time of enrollment (Uncontrolled with insulinand oral medications, HbA1c ≥ 8.0% or fasting blood sugar ≥ 200 mg/dL)

9. Patients with uncontrolled hypertension at the time of enrollment (systolic pressure > 150 mmHg or diastolic pressure >100 mmHg) despite use of antihypertensiveagent

10. Patients with uncontrolled heart disease (severe heart failure, unstable angina,uncontrolled arrhythmia, or history of life-threatening arrhythmia, etc.)

11. Patients with hereditary problems such as galactose intolerance, Lapp lactasedeficiency or glucose-galactose malabsorption, etc.

12. Patient with known active or uncontrolled HIV, tuberculosis, hepatitis B, orhepatitis C infection

13. Pregnant or lactating women

14. Patients who do not agree to use effective contraception during treatment period andfor at least 5 months after the end of IP administration

15. Patients who received herbal medicine within 4 weeks before the first administrationof IP (Bojungikgitang) and been decided that such intake affect the trial or safetyof the subject at the investigator's discretion

16. Patients who received other investigational drugs within 30 days before the firstadministration of IP (Bojungikgitang)

17. Severe hypersensitivity to IP and its components (rash, redness, hives, eczema,dermatitis, itching, etc.)

18. Patients who are not eligible for the trial at the discretion of the investigatorincluding severe infectious diseases or organ failure, etc.