YIV-906 (Formerly PHY906/KD018) With Sorafenib in HBV(+) Hepatocellular Carcinoma (HCC)

Prior treatment

• Patients who have received systemic chemotherapies or immunotherapy or molecular target therapies or anticancer Chinese medicine Cinobufacini
• Patients who have received any local anti-cancer therapy within 4 weeks prior to Cycle 1 treatment
• Active bleeding (including gastrointestinal bleeding) during the last 4 weeks prior to Cycle 1 treatment
• Patients receiving chronic treatment with corticosteroids (except for intermittent topical or local injection of aldosterone) or other immunosuppressive agents (oral prednisone or equivalent 10 mg/day is allowed to screen).
• Patients treated with drugs known to be strong inducers of isoenzyme CYP3A within 7 days of Cycle 1 treatment
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from surgery
• Patients who have received an investigative drug or therapy within the last 4 weeks prior to Cycle 1 treatment
• Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection
• Patients taking traditional Chinese medicines within 14 days prior to taking first dose of study treatment

Other illness

• Patients who ever have HCV infection
• Patients with a history of allergy to the known components of YIV-906
• Known history of human immunodeficiency virus (HIV) seropositivity
• Active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma-in-situ of the cervix) within the past 5 years
• Ongoing or recent history of autoimmune, uncontrolled psychiatric disorders and drug abuse
• Uncontrolled hereditary or acquired thrombotic or bleeding disorder

Lab values

• Any severe and/or uncontrolled medical conditions including but not limiting:
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to Cycle 1 treatment, serious uncontrolled cardiac arrhythmia, uncontrolled hypertension
  • Previous transient ischemic attack (TIA), cerebral vascular accident (CVA), symptomatic peripheral vascular disease (PVD) within last 6 months of Cycle 1 treatment
  • Congenital long QT syndrome
  • Alcoholic patients
  • Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy, in the opinion of the investigator, except chronic HBV
  • Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
  • Patients who have had organ transplantation
• Patients received any blood transfusion, albumin transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), TPO or other medical supportive treatment within 4 weeks of Cycle 1 treatment
• Chronic therapy with nonsteroidal anti-inflammatory agents or other anti-platelet agents. Aspirin at doses up to 100 milligrams/day is permitted

Age

• Men and women of childbearing age and potential, who are not willing to use effective contraception

Other

• Patient who has any of the following criteria will be excluded from the trial:
• Known central nervous system metastasis including brain metastasis and meningeal carcinomatosis
• Hepatocholangiocarcinoma, fibrolamellar cell carcinoma and mixed hepatocellular carcinoma
• Pregnant and/or breastfeeding women
• Unwilling or unable to follow protocol requirements or to give informed consent
• Therapeutic dose anticoagulation with warfarin, or similar agents
• No patient, however, may enroll in this trial if they are taking phenytoin (Dilantin)

• Male or females ≥18 years old with ability to take oral drugs
• Diagnosis of advanced (locally advanced or metastatic) unresectable/inoperable HCC according to the American Association for the Study of Liver Diseases (AASLD) Guidelines (Heimbach et al. 2018) or diagnosis by tissue pathology
• Participants categorized to stage B or C based on Barcelona Clinic Liver Cancer (BCLC) staging system
• Life expectancy of at least 3 months
• Presence of chronic hepatitis B (HBsAg (+))
• Never received systemic antitumor therapy
• Patients must have at least one tumor lesion that meets both of the following criteria:
  • "Measurable disease" according to RECIST1.1, i.e. at least one measurable lesion.
  • Advanced unresectable HCC that have liver limited disease who have failed and are not candidates to local therapies; or patients with extrahepatic disease.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Cirrhotic status of current Child-Pugh class A. Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period
• For patients with positive HBV-DNA and positive HBsAg, they must be treated with anti-HBV treatment (per local standard of care), as prophylaxis starting at least 1-2 weeks prior to receiving study drug and willing to continue treatment for the length of the study
• Patients with adequate organ reserve, such as laboratory parameters:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 10\^9/L
  • Platelets ≥ 60000 x 10\^6/L
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Serum alanine amino-transferase (ALT) ≤ 5 x ULN
  • Serum Aspartate transaminase (AST) ≤ 5 x ULN
• Adequate renal function, based upon meeting the following laboratory criteria within 7 days before randomization:
  • Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40mL/min (using the Cockcroft-Gault equation: (140-age) x weight (kg)/ (serum creatinine x 72 \[mg/dL\] for males. (For females multiply by 0.85) AND
  • Urine protein/creatine ratio (UPCR) ≤ 1 mg/mg (≤113.1 mg/mmol) or 24-hour urine protein \<1 g
• Ability to understand and willingness to sign a written informed consent and to be able to follow the visit schedule