Safety and Potential Efficacy of MS-20 In Combination With Pembrolizumab for the Treatment of NSCLC

Overview

MS-20 was approved as the first oral cancer adjuvant new drug indicated for ameliorating fatigue and appetite loss associated with cancer chemotherapy via reshaping human gut ecosystem and restoring immunity. MS-20 has also been shown to be anti-PD-1 booster by activating tumor-infiltrating lymphocytes (TILs) in mice cancer models, particularly promoting migration of TILs into tumors and increasing the amount of TILs inside tumors. Therefore, this study is designed to explore the safety and relationship between gut microbiome and potential clinical outcomes in NSCLC patients under combination therapy with pembrolizumab and MS-20.

Eligibility

Inclusion Criteria:

1. Male or female subjects who are over 20 years old (inclusive) at the time of signing the informed consent form.
2. The subject is diagnosed pathologically or cytologically with non-small cell lung cancer(NSCLC).
3. According to the 8th edition of the American Joint Committee on Cancer [AJCC], it is classified as metastatic stage IV NSCLC.
4. The subject with metastatic non-small cell lung cancer whose EGFR/ALK/ROS 1 tumor gene is wild type.
5. At least one measurable lesion per RECIST v 1.1 criteria.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. The subject whose biomarker performance: The PD-L1 performance detected by Dako 22C3 or Ventana SP263 and other third-level in vitro diagnostic medical devices (class III) must meet tumor proportion scores (TPS) ≥ 50%.
8. The life expectancy is not less than 3 months.
9. The subject whose liver and kidney functions must meet all of the following

   conditions

   • Liver function: aspartate aminotransferase (AST) value < 2.5 x ULN, alanine aminotransferase(ALT) value < 2.5 x ULN and total bilirubin (T-bilirubin) value < 1.5 x ULN. For the subjects who have liver metastases, total bilirubin value should be < 5 x ULN.
   • Kidney function: Serum creatinine value < 1.5 x ULN. If subject's serum creatinine value is ≥ 1.5 x ULN, his/her creatinine clearance value should be > 40 mL/min based on Cockcroft and Gault formula.

10. Subject, if a female of child-bearing potential, must agree to completely abstain from

    sexual intercourse or be willing to use appropriate methods of contraception (e.g., Intra-uterine device or contraceptives) during the study. 【The definition of infertile：(1) Being menopause for more than 1 year；(2) Surgery for permanent contraception (e.g., abdominal tubal sterilization, bilateral Salpingo-Oophorectomy, and tubectomy)；(3) Congenital structural abnormalities.】

11. Subject, if male, agrees not to donate sperm, be willing to avoid sexual intercourse or use appropriate contraception method (e.g., using a condom) during the study treatment period.
12. Subject is active and capable to communicate with site staff, willing to be in compliance with the following two items based on investigator's judgment.

        (1) To complete return visits and study examination per the study protocol. (2) To collect
        stool specimens at home, refrigerate and deliver the sample.
        Exclusion Criteria:
          1. Presence of any symptomatic central nervous system metastasis or leptomeningeal
             metastasis which has not been treated or is under disease progression. For subjects
             with brain metastasis who have been treated and confirmed as stable per radiology
             diagnosis, which means no evidence of disease progression based on repeated CT scan
             with at least a 4-week window period (Note: The repeated angiography should be within
             the study screening period and before receiving the investigational drug), could be
             enrolled if his/her clinical condition is stable and not using steroid treatment for
             at least 14 days before study treatment.
          2. Presence of any other malignant tumor. Unless the subject had completed radical
             treatment without any disease recurrence for at least 3 years. (Those who have
             successfully undergone radical resection or have received possible curative treatments
             for basal cell carcinoma, superficial bladder cancer, squamous-cell carcinoma,
             cervical intraepithelial neoplasia or other carcinoma in situ are not limited)
          3. Presence of any autoimmune disease which requires systemic treatment within the past 2
             years. Hormone replacement therapy (for example, insulin or physiological replacement
             of corticosteroid due to adrenal or pituitary disorders, etc.) is allowed and not
             considered as systemic treatment.
          4. Have had any transplantation of allogeneic cells, tissue, or solid organ.
          5. History of known human immunodeficiency virus (HIV) infection.
          6. Hepatitis B surface antigen (HBsAg) is positive or hepatitis B virus (HBV) DNA viral
             load is ≥500 IU/mL.
          7. Hepatitis C virus (HCV) antibody is positive and hepatitis C virus (HCV) ribonucleic
             acid(RNA) is also positive.
          8. Subject has non-infectious pneumonia history which requires systemic steroids or who
             currently have interstitial pneumonia or interstitial pneumonitis.
          9. Presence of any severe cardiac dysfunction, Class III-IV of chronic heart failure
             based on New York Heart Association (NYHA) Functional Classification, which includes
             symptomatic coronary artery disease and severe ventricular arrhythmia; Presence of any
             myocardial infarction, unstable or poorly controlled angina within 6months before
             subject screening visit (V0).
         10. Have any gastrointestinal history or surgery which the investigator believes may
             affect the absorption of the oral investigational product.
         11. Enterocutaneous or non- enterocutaneous fistula which is defined as Grade 3 or above
             based on Common Terminology Criteria for Adverse Events (CTCAE, also known as Common
             Toxicity Criteria).
         12. Currently presence of inflammatory bowel disease or gastric ulcer.
         13. Have not yet recovered from major surgery or complications before subject screening
             visit(V0).
         14. History of active tuberculosis (TB, Mycobacterium tuberculosis).
         15. Presence of any mental disease or drug abuse disorder that may interfere with
             subject's ability for being compliant with study requirements.
         16. Active infection which requires systemic treatment.
         17. Allergies to soy products, severe allergies to antibody therapy, or known allergies or
             intolerances to any component of pembrolizumab.
         18. Have previously received systemic chemotherapy or other targeted or biological
             anti-tumor treatments for metastatic NSCLC.
         19. Have received anti-PD-1, anti-PD-L1, or anti-PD-L2 drug therapy within 3 years before
             the screening visit (V0) or act on another drug treatment that stimulates signals or
             synergistically inhibits T cell receptors (e.g. CTLA-4, OX 40, CD137).
         20. Received radiotherapy within the 14 days before receiving the investigational drug or
             received pulmonary radiotherapy> 30 Gy within 6 months before receiving the
             investigational drug (the subject must recover from all radiation-related toxicities
             to grade 1 or below, without corticosteroid therapy and radiation pneumonia has never
             occurred).
         21. Diagnosed with immunodeficiency or are receiving any form of immunosuppressive
             therapy, systemic steroids (allowed to use up to 10 mg Prednisone or equivalent
             steroids per day) within 7 days before receiving the investigational drug.
         22. Those who have received live-virus vaccines within 30 days before receiving the
             investigational drug or are expected to receive live-virus vaccines during the study
             period.
         23. Have used antibacterial drugs including antibiotics and synthetic drugs (such as
             sulfonamides, quinolones), antifungal or antiviral drugs (not including topical
             medication) within the 14 days before receiving the investigational drug.
         24. Use probiotics and prebiotics-related products within 14 days before receiving the
             investigational drug. (e.g., yogurt drink, yogurt, Yakult, probiotic fermented
             beverages, Wakamoto tablets, Shin Biofermin S tablets, inulin, oligosaccharide
             products, etc.)
         25. Those who have had gastrointestinal infection and diarrhea within the 14 days before
             receiving the investigational drug (soft or watery stools more than three times within
             24 hours).
         26. Women who are pregnant, breastfeeding, or expect to breastfeed during the study
             period.
         27. Currently participating in clinical trials of other investigational product
             treatments, medical devices, health foods, or cosmetics.
         28. Subjects who judged by the investigator to be unsuitable to participate in the trial.