ABSK-011+BSC vs. Placebo+BSC in Previously Treated Advanced HCC With FGF19 Overexpression

Prior treatment

• Known allergies or hypersensitivity to any component of the investigational product (ABSK-011 or placebo).
• Previous treatment with selective FGFR4 inhibitors.
• Previous anti-tumor therapy is ≤ 4 weeks from randomization.
• Major surgery within 4 weeks prior to randomization; or any surgical wound infection, dehiscence, or incomplete healing within 2 weeks prior to randomization; Or major surgery is planned during study treatment.
• Toxicities caused by prior chemotherapy, radiotherapy, and other anti-tumor therapies (including immunotherapy) did not recover to ≤ Grade 1 CTCAE v5.0.
• Active or documented gastrointestinal bleeding within 6 months prior to screening.
• Patients with intractable/uncontrolled pleural or pericardial effusion requiring intervention within 2 weeks prior to randomization and clinically significant ascites.
• Prior or current hepatic encephalopathy (any grade).
• Previous organ transplant and anti-rejection drug therapy indicated.
• The factors that significantly affect the absorption of oral drugs.
• Receipt of P-gp transporter inhibitors or moderate, strong inhibitors or inducers of CYP3A4 within 2 weeks prior to randomization.
• Any serious acute or chronic infection requiring systemic antibacterial, antifungal, or antiviral therapy within 2 weeks prior to randomization.

Other illness

• History of second primary malignancies other than HCC within the first 5 years of screening.
• Imaging revealed HCC involving the main portal vein (Vp4), inferior vena cava, superior vena cava, superior mesenteric vein, or heart.
• Impaired cardiac function or clinically important heart disease.
• Patients coinfected with HBV and HCV.
• Known acquired immunodeficiency syndrome (AIDS) -associated disease or tested positive for HIV 1/2 antibodies.
• Patient who cannot be assessed by contrast-enhanced CT and/or MRI due to allergy to computed tomography (CT) and/or magnetic resonance imaging (MRI) contrast media or other contraindications.

Other

• Known fibrolamellar HCC, sarcomatous HCC, or mixed hepatocellular carcinoma-cholangiocarcinoma.
• Liver tumors as a percentage of whole liver ≥ 50% as judged by the investigator.
• Presence of meningeal or central nervous system (CNS) metastases.
• Any other clinically significant comorbidities may affect the patient's health or safety, affect the signing of informed consent, affect protocol compliance, or interfere with the interpretation of the study results.

• Patients should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patients should be able and willing to comply with study visits and procedures as per protocol.
• Patients (male or female) ≥ 18 years of age at the time of signing the informed consent form.
• Patients with advanced or unresectable HCC confirmed histologically/cytologically or clinically according to the American Association for the Study of Liver Diseases (AASLD) criteria (for patients with cirrhosis).
• Have received at least one prior PD- (L) 1 inhibitor approved as a single agent or in combination for the treatment of HCC and at least one mTKI approved for the treatment of HCC.
• BCLC stage B(ineligible for local or radical therapy, or relapse or progression of disease after local therapy or radical therapy) or C.
• Child-Pugh class A.
• Positive for FGF19 overexpression.
• At least 1 measurable lesion meeting RECIST v1.1 criteria.
• ECOG performance status 0 or 1.
• Life expectancy ≥ 3 months.
• Adequate control of blood pressure (BP) at screening.
• Adequate organ function and bone marrow function.
• Non-surgically sterilized male or female patients of childbearing potential must agree to use reliable contraception for at least 2 weeks prior to randomization until 1 month after the last dose of study treatment.