This is a randomized, double-blind, multicenter, Phase 2 study to evaluate the efficacy and safety of ABSK-011 plus BSC versus placebo plus BSC in advanced or unresectable hepatocellular carcinoma (HCC) patients with FGF19 overexpression who have received prior systemic therapy. Approximately 141 advanced or unresectable HCC patients with FGF19 overexpression who have received prior systemic therapy will be enrolled and randomized to experimental arm or control arm in a 2:1 ratio. Patients will receive assigned study treatment, every 28-day treatment cycle within 1 day of randomization until disease progression, intolerable toxicity, start of new anti-tumor therapy, death, patient refuse to continue treatment, loss to follow-up, or other reasons leading to treatment discontinuation. Immediate BICR review is required for patients with radiographic disease progression as assessed by the investigator. If disease progression is assessed by BICR, the investigator is allowed to unblind after disease progression according to the protocol-specified procedures. After unblinding, patients in the experimental arm, study drug should be discontinued. Patients in the control arm may be transferred to receive ABSK-011 plus BSC after assessment.
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.
Known allergies or hypersensitivity to any component of the investigational product (ABSK-011 or placebo).
Previous treatment with selective FGFR4 inhibitors.
Known fibrolamellar HCC, sarcomatous HCC, or mixed hepatocellular carcinoma-cholangiocarcinoma.
Previous anti-tumor therapy is ≤ 4 weeks from randomization.
Parallel
ABSK-011+BSC
DrugABSK-011 capsules will be provided and should be taken twice daily, with an interval of approximately 12 hours. The investigational product should be taken with food, with approximately 150 mL of water.
Placebo+BSC
DrugPlacebo capsules will be provided and should be taken twice daily, with an interval of approximately 12 hours. The investigational product should be taken with food, with approximately 150 mL of water.
ORR by BICR
Objective response rate (ORR) assessed by Blinded Independent Central Review (BICR) per RECIST v1.1, defined as the proportion of patients achieving complete response (CR) or partial response (PR). Patients who receive crossover treatment or start a new anti-tumor therapy prior to achieve an objective response (PR or CR) will be considered as non-responders.
PFS
Defined as the time (months) from randomization to disease progression or death due to any cause, whichever occurs first.
DOR
Defined as the time (months) from the first documented objective response to disease progression or death due to any cause, whichever occurs first.
DCR
Defined as the proportion of patients achieving CR, PR, or SD (meeting the minimum criteria for SD lasting at least 6 weeks).
TTP
Defined as the time (months) from randomization to disease progression.
Levels of FGF19 in blood samples
Changes in selected PD markers before and after treatment.
Cmax
maximum observed concentration
Tmax
time to maximum observed concentration
AUC
area under the concentration-time curve
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