AHCC® as Immune Modulator in Cancer Patients Treated With Immunotherapy

A Standardized Extract of Cultured Lentinula Edodes Mycelia (AHCC®) as Immune Modulator in Cancer Patients Treated With Immunotherapy: a Phase 2 Double-blind, Randomized, Placebo-controlled Trial

This is a prospective, double-blind, randomized, placebo-controlled trial to evaluate whether AHCC® (Active Hexose Correlated Compound) can enhance the effect of immunotherapy in liver cancer patients.

Objectives:

Assess the potential of AHCC® to improve immunotherapy outcomes Evaluate progression-free survival (PFS) Evaluate overall survival (OS) Assess safety and tolerability

Method:

Participants will take 3 grams of AHCC® or placebo orally each day Treatment will continue until disease progression, treatment intolerance or other treatment options become available.

Note:

AHCC® is a novel functional food with immune-modulating potential.

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 been treated 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 (either Cockcroft-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 or tenofovir, according to current practice guidelines) before start of study drug treatment.

Exclusion Criteria:

• 1.Major systemic diseases that the investigator considers inappropriate for participation.
• 2.Any active autoimmune disease or history of known autoimmune disease except for vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• 3.Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
• 4.Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
• 5.Requirement of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• 6.Prior organ allograft or allogeneic bone marrow transplantation.
• 7.Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation and in the judgment of the investigator would make the patient inappropriate for entry into this study.