AHCC® as Immune Modulator in Cancer Patients Treated With Immunotherapy

Inclusion Criteria:

• 1.Liver cancer patient who will receive immunotherapy

• 2.At least one measurable tumor, according to RECIST version 1.1, that has not beentreated with any local procedure.

• 3.Age >=20 years old.

• 4.ECOG performance status 0 or 1.

• 5.White blood count >=2,000/microliter ; platelet count >=60,000/microliter.

• 6.Liver transaminases (ALT and AST) <=5 times upper limit of normal values (ULN);total bilirubin <= 2 times ULN; creatinine clearance or eGFR > 50 mL/min (eitherCockcroft-Gault or MDRD is acceptable, whichever is higher).

• 7.Subjects with chronic hepatitis B virus infection (HBV surface antigen (HBsAg)positive) must start antiviral therapy with nucleoside analogs (e.g., entecavir ortenofovir, according to current practice guidelines) before start of study drugtreatment.

Exclusion Criteria:

• 1.Major systemic diseases that the investigator considers inappropriate forparticipation.

• 2.Any active autoimmune disease or history of known autoimmune disease except forvitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residualhypothyroidism due to autoimmune condition only requiring hormone replacement,psoriasis not requiring systemic treatment, or conditions not expected to recur inthe absence of an external trigger are permitted to enroll.

• 3.Dementia or significantly altered mental status that would prohibit theunderstanding or rendering of informed consent and compliance with the requirementsof this protocol.

• 4.Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any otherantibody or drug specifically targeting T-cell costimulation or checkpointpathways).

• 5.Requirement of systemic treatment with either corticosteroids (> 10 mg dailyprednisone equivalents) or other immunosuppressive medications within 14 days ofstudy drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of activeautoimmune disease.

• 6.Prior organ allograft or allogeneic bone marrow transplantation.

• 7.Other severe acute or chronic medical or psychiatric condition, or laboratoryabnormality that may increase the risk associated with study participation and inthe judgment of the investigator would make the patient inappropriate for entry intothis study.