Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma

An Open-Label, Single-Arm, Two-Stage, Multi-Centre Phase II Study to Evaluate the Efficacy and Safety of TLC388 as Second-line Treatment in Subjects With Advanced Hepatocellular Carcinoma

The purpose of this study is to evaluate the safety and efficacy of TLC388 (Lipotecan) as a second line treatment in subjects with advanced Hepatocellular Carcinoma.

A Phase II, open-label, single-arm, two-stage, multicenter study to evaluate the efficacy and safety of Lipotecan® monotherapy in patients with advanced hepatocellular carcinoma (HCC) and had failed sorafenib treatment due to sorafenib intolerance or radiographic progressive disease (PD).

Eligible patients received 40 mg/m2 of Lipotecan®, given as a 30-minute (+3 minutes) intravenous infusion, on Days 1, 8, and 15 of a 28-day cycle for maximum 6 cycles. Inter-cycle and intra-cycle dose delays were allowed within 21 days of the scheduled date to be reduced to 35 mg/m2 and further to 30 mg/m2 if a treatment-related adverse event (TRAE) met the criteria for dose reduction.

Tumor response was assessed every 2 cycles until Cycle 6, or at the early termination according to RECIST Version 1.1 judged by site investigator. The favorable response of CR, PR or SD would be confirmed within 28-35 days. Safety evaluations were conducted on a weekly basis from the day study treatment administered throughout each cycle.

Inclusion Criteria:

• Radiological diagnosis of hepatic tumor(s) by contrast-enhanced study
• Subjects with advanced HCC who are not eligible for surgical resection or loco-regional therapy.
• Subjects with sorafenib treatment failure due to sorafenib intolerance or radiographic PD (as per RECIST v1.1). Prior sorafenib use should be ≥ 400 mg/day for at least 14 days.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Child Pugh Score ≤ 6;
• A life expectancy of at least 12 weeks or more

Exclusion Criteria:

• Subjects who have received any systemic target therapy or systemic chemotherapy other than sorafenib for the treatment of HCC.
• Subjects who have received sorafenib within 2 weeks prior to the initiation of the treatment dose, or have any sorafenib-related toxicities not yet resolved to grade 1 or baseline.
• Subjects who have undergone liver transplantation surgery.
• Major surgery within 4 weeks prior to the initiation of the treatment dose (excluding implantation of the intravenous infusion device). Percutaneous liver puncture within 2 weeks prior to the initiation of the treatment dose.