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

• Status: Recruiting
• Trial end date: 2022-02-28
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to compare the efficacy and safety of YIV-906 plus standard-of-care sorafenib versus those of sorafenib alone as a first-line systemic treatment for patients with Hepatitis B (+) associated advanced hepatocellular carcinoma.

YIV-906 (PHY906, KD018) is an immune system modulator. Clinical and preclinical research suggests that YIV-906 could act to enhance the body's immune response to fight cancer and increase the anti-tumor activity of sorafenib and protect and repair the gastrointestinal tract by reducing inflammation and promoting tissue regeneration.

Inspired by a 1,800-year-old traditional medicine still in use today, YIV-906 is a botanical drug candidate, composed of an extract of four herbs and administered in oral capsule form.

The CALM (Combination of YIV-906 and Sorafenib to treat Advanced Liver cancer in a Multi-center study) trial is a multi-regional, randomized, placebo-controlled study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yiviva Inc.
• Treatments: Sorafenib

Criteria

Inclusion Criteria:

• Male or females ≥ 18 years old with the ability to take oral drugs

• Diagnosis of advanced HCC according to the American Association for the Study of Liver Diseases (AASLD) Guidelines (Heimbach et al. 2018) or diagnosis by tissue pathology

• Life expectancy of at least 3 months

• Presence of chronic hepatitis B (HBsAg (+) and IgM anti-HBc (-))

• Never received systemic antitumor therapy

• Patients must have at least one tumor lesion that meets both of the following criteria:

• "Measurable disease" according to RECIST 1.1 , i.e. at least one measurable lesion.

• Advanced unresectable HCC that have liver limited disease who have failed or not candidates to local therapies including surgery and local-regional 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/or positive HBsAg results, they must be treated with antivirals (per local standard of care), as prophylaxis starting at least 1-2 weeks prior to receiving study drug and willingness 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

• 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 Cockroft-Gault equation: (140-age) x weight (kg)/(serum creatinine x 72 [mg/dL] for males. (For females multiply by 0.85) AND

• 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

Exclusion Criteria:

• Patients who ever have HCV infection

• Patients who have received systemic chemo-therapies or immunotherapy or molecular target therapies

• Patients who have received any local anti-cancer therapy within 4 weeks prior to Cycle 1 treatment

• Active bleeding (including gastrointestinal bleeding, encephalopathy, and ascites) during the last 4 weeks prior to Cycle 1 treatment

• Patients with a history of allergy to the known components of YIV-906

• Known history of human immunodeficiency virus (HIV) seropositivity

• Known central nervous system metastasis including brain metastasis and meningeal carcinomatosis

• Hepatocholangiocarcinoma, fibrolamellar cell carcinoma and mixed hepatocellular carcinoma

• 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

• Any severe and/or uncontrolled medical conditions including but not limiting to:

• 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 this study therapy, in the opinion of the investigator, except chronic HBV

• Impairment of gastrointestinal function or who have a 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 receiving chronic treatment with corticosteroids (except for intermittent topical or local injection or aldosterone) or other immunosuppressive agent Subjects receive any blood transfusion, albumin transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), TPO or other medical supportive treatment prior to Cycle 1 treatment

• 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 investigational drug or therapy within the last 4 weeks prior to Cycle 1 treatment.

• Pregnant and/or breastfeeding women

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

• Unwilling or unable to follow protocol requirements or to give informed consent

• An ongoing or recent history of autoimmune, uncontrolled psychiatric disorders and drug abuse

• Uncontrolled hereditary or acquired thrombotic or bleeding disorder

• Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection

• Therapeutic dose anticoagulation with warfarin or similar agents

• Chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents. Aspirin at doses up to 100 milligrams/day is permitted

• Patients with an estimated or calculated baseline creatinine clearance of less than 40 mL/min should not be enrolled in this trial

• No patient, however, may enroll in this trial if they are taking phenytoin (Dilantin)

• Patients taking traditional Chinese medicines within 14 days prior to taking first dose of study treatment