Phase 2 Study of WGI-0301 for Advanced HCC

Exclusion Criteria35

• Pregnant or breastfeeding patients or expecting to conceive or father children within the projected duration of the study.
• Stage 2 and Stage 3: Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
• Complete occlusion of the major portal vein or vena cava due to HCC (The major portal vein is defined as the part of portal vein between the union of the splenic and superior mesenteric veins and the first bifurcation into the left and right vein).
• Major surgery within 4 weeks prior to the first dose of study intervention.
• Previous identified allergy or hypersensitivity to components of WGI-0301 similar drugs or liposomal drugs or related excipients.
• Stage 2 and Stage 3: Previous identified allergy or hypersensitivity to components of Sorafenib or similar drugs.
• Stage 3 only: Received prior Sorafenib therapy or any agents targeting AKT-PI3K pathway.
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study intervention (except for observational clinical trials).
• Locoregional therapy to liver within 4 weeks prior to the first dose, including but not limited to TACE, radiotherapy, radiofrequency ablation, microwave (except palliative radiotherapy for bone pain relief completed at least 2 weeks prior to the first dose).
• Small molecule targeted therapy and traditional Chinese medicine with antitumor indications received within 2 weeks prior to the first dose, or chemotherapy, biological therapy, and other antitumor treatments received within 4 weeks prior to the first dose.
• Stage 2 and Stage 3：Patients on concomitant use of strong CYP3A4 inducers (see Appendix 3 in Section 14.3) within 12 days prior to the first dose of study intervention.
• Clinically significant abnormalities of glucose metabolism (e.g., Patients with diabetes mellitus type1 or diabetes mellitus type 2 requiring treatment, or those with HbA1c ≥8.0%.
• Clinically significant cardiovascular disease including:
• Uncontrolled chronic hypertension defined as systolic \> 150 mmHg or diastolic \> 90 mmHg on more than one measurement despite optimal therapy (initiation or adjustment of BP medication prior to study entry is allowed provided that the average of 3 BP readings prior to enrollment is \< 150/ 90 mmHg).
• Hypotension as indicated by systolic blood pressure \< 90 mmHg or mean arterial pressure \< 65 mmHg on 2 consecutive measurements at the Screening Visit.
• NYHA class III or IV Congestive heart failure, myocardial infarction or stroke, unstable angina pectoris, pericardial effusion (excluding trace pericardial effusion identified by echocardiography), or left ventricular ejection fraction \< 45% within 6 months prior to the first dose.
• Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy).
• Bradycardia (known history of cardiovascular disease and either physical examination at rest or electrocardiogram indicating heart rate \< 50 bpm), or screening ECG indicating QTcF \> 470 msec, 2 retests were required for the first abnormal QTcF , and 3 mean values were taken. Or there is severe arrhythmia requiring further treatment, including but not limited to ventricular fibrillation, atrial fibrillation, sustained ventricular tachycardia, second-degree or third-degree atrioventricular block, torsades de pointes, etc.
• Stage 2 and Stage 3: Clinically significant gastrointestinal disorders including:
• Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/ or absorption of the tested products
• Gastrointestinal perforation and/ or fistula intra-abdominal abscess or intestinal obstruction within 6 months prior to the first dose
• Clinically significant gastric bleeding within 6 months prior to the first dose (patients may be enrolled if esophageal and gastric varices are present on imaging, but no bleeding event or inpatient medical intervention occurs within 6 months prior to the first dose)
• Clinically significant bleeding risks including:
• Known hereditary or acquired bleeding or thrombotic tendencies (e.g., hereditary hemorrhagic telangiectasia or von Willebrand disease)
• Bleeding symptoms such as hemoptysis (\> 1/ 2 teaspoon bright red blood) and gastrointestinal bleeding within 3 months prior to screening
• Thrombolytic agents within 10 days prior to the first dose
• Receiving anticoagulant therapy (e.g., anticoagulants, antiplatelets), and subject 's INR and APTT are not within expected therapeutic range of anticoagulant (except sodium heparin for maintenance of central venous catheter patency)
• History of solid organ transplant.
• Known HIV or AIDS related illness or is receiving systemic steroid therapy (physiological doses of hormones, such as prednisone \<10 mg/day or equivalent doses of similar corticosteroids are acceptable) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
• Known active or uncontrolled infection that could interfere with the study (such as requiring intravenous antibiotics, antiviral or antifungal medications).
• Uncontrolled ascites or pleural effusion requiring repeated drainage (Investigator 's judgment).
• Past or current history of neoplasm other than HCC, except for curatively treated nonmelanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 3 years.
• Known CNS or brain metastasis that is either symptomatic or untreated (except for asymptomatic cases not requiring treatment).
• History of drug abuse or addiction at the present stage.
• Subject has any other conditions or reason that, in the opinion of the Investigator, interferes with the ability of the subject to participate in the trial, places the subject at undue risk or complicates the interpretation of data.