Liver Cancer Clinical Trials

• ≥18 years of age on the day of signing informed consent, male or female.

• Voluntarily agree to provide signed informed consent and are willing and able to comply with all aspects of the protocol.

• Histologically or cytologically confirmed diagnosis of HCC, or clinical diagnosis of HCC as per 2018 AASLD criteria.

• BCLC Stage C or BCLC Stage B with bilobar involvement and infiltrative nature that is only suitable for systemic anti-tumor therapy, and not suitable for any curative surgeries, liver transplantation, or local therapy (BCLC Classification see Appendix 6, Section 14.6).

• Stage 1 only: At least first-line standard treatment failure (disease progression confirmed by imaging) with no available standard treatment options, or unsuitability for standard treatment, or intolerance to standard treatment.

• Stage 2 only: At least first-line standard treatment failure (disease progression confirmed by imaging) or intolerance.

• Stage 3 only: Patients must have objective radiographic disease progression or intolerance (Intolerance is defined as currently discontinued after ≥28 days of treatment due to toxicity) after only one prior line of systemic immunotherapy treatment with an anti-PD-1/ PD-L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies (Prior locoregional therapy such as surgery, radiofrequency ablation or trans-arterial chemoembolization are also allowed but not counted as systemic therapy, provided that progression has been documented after these therapies, and ≥4 weeks have elapsed since the last therapy).

• Stage 2 and Stage 3: Eligible for treatment with Sorafenib as determined by investigators according to the Package Insert and clinical judgment.

• ECOG PS of 0 or 1 within 7 days prior to the first dose of study intervention.

⁃ Patients must have at least one measurable lesion according to RECIST 1.1 as determined by the investigator, and that has not been the target of local or regional therapy including trans-arterial chemoembolization, intra-arterial chemotherapy, ethanol, or radiofrequency ablation; a new area of tumor progression within or adjacent to a previously treated lesion, if clearly measurable by a radiologist, is acceptable.

⁃ Life expectancy in the judgement of the Investigator \> 12 weeks.

⁃ Recovery to ≤Grade 1 (CTCAE V5.0) from toxicities related to any prior treatments unless the adverse events are clinically non-significant and/ or stable on supportive therapy, such as alopecia, Grade 2 peripheral neuropathy, and hypothyroidism stabilized on hormone replacement therapy.

⁃ Stage 2 and Stage 3:Collection of an archived tissue sample will be requested (where available) or agree to undergo tumor tissue biopsy for biomarker testing; however, a subject will not be precluded from participating in the study if tissue sample is not available for collection or is otherwise insufficient for analysis.

⁃ Patients must have adequate organ function as defined below:

∙ Child-Pugh Liver Function Class A or Class B (score ≤ 7) (see Appendix 7 in Section 14.7)

‣ AST and ALT ≤ 3.0 × ULN and total bilirubin ≤ 2 × ULN

‣ Serum albumin ≥ 2.8 g/ dL

‣ CrCL ≥ 40 ml/ min (Cockcroft-Gault formula: CrCL (mL/ min) = \[140-age(year)\] × body weight (Kg)/ \[72 × Scr (mg/ dl)\]{ × 0.85 for female subjects})

‣ INR ≤ 2.0 (except for warfarin therapy)

‣ Hemoglobin ≥ 8.5 g/ dL, absolute neutrophil count \> 1000/ mm3, platelet count ≥ 60 000/ mm3(no blood transfusion, blood products, cell growth factors, albumin or any other corrective therapeutic drugs within 14 days)

⁃ Participants with HBV or HCV infection will be allowed if they meet the following criteria:

∙ HBV-HCC: Resolved HBV infection (as evidenced by detectable HBV surface antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable HBV surface antigen) or chronic HBV infection (as evidenced by detectable HBV surface antigen or HBV DNA). Subjects with chronic HBV infection must have HBV DNA \< 500 IU/ mL and must should be managed according to treatment guidelines. Those on antiviral therapy at screening should have been treated for \>2 weeks before the first dose.

‣ HCV-HCC: Resolved HCV infection (as evidenced by detectable HCV RNA or antibody), or stable HCV infection (such as normal LFTs or being asymptomatic). Patients with positive HCV RNA requiring direct antiviral agent treatment, or those with HBV and HCV co-infection are excluded.

⁃ WOCBP must have a negative serum pregnancy within 3 days prior to receiving the first dose of study medication and must use accepted highly effective methods of contraception from the time of signing the informed consent through 6 months after the last dose of study drug. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, or be surgically sterile, for the duration of study participation, and for 3 months after completion of study drug administration. See Appendix 1 for protocol-approved highly effective methods of contraceptive combinations.